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Biomedical subjects

R Herrmann

Publications and source records attributed to R Herrmann.

At least 127 records · Page 7Linked to original sources
PubMed1998

Intra-atrial defibrillation for atrial fibrillation: animal data.

Animal research in the area of atrial defibrillation has helped to bring about a greater understanding of the mechanisms and influencing factors of atrial defibrillation. Increased clinical interest in atrial tachyarrhythmias during the 1980s led to more intensive animal research in this area, in which concepts of intra-atrial cardioversion was only first described in 1974. Initially, the concept of one intracardiac catheter in conjunction with a subcutaneous electrode was evaluated. Further studies involved alternative waveforms, shock durations, electrode materials, and lead configurations to improve the percentage of successful cardioversions while reducing energy requirements. The results from ventricular defibrillation, in which the need for a homogenous field through the majority of fibrillating mass had been established, were applied to research for atrial defibrillation as well. An intracardiac vector with electrodes inside the heart was determined to be most efficient. Results concerning the feasibility, efficacy, and safety have been confirmed by clinical data. Further animal studies will help to evaluate new concepts for reducing energy requirements, such as new electrode materials and advanced shock timing. The clinical benefits of basic research in internal cardioversion of atrial fibrillation justifies additional animal research studies.

Atrial Fibrillation↗
PubMed1997

Estimation of the environmental contamination by phthalic acid esters leaching from household wastes.

Phthalic acid esters (PAE) have been used as plasticizers in many products. Here we estimate the contaminating potential of PAE codisposed with domestic wastes. In order to determine the maximum threat to the environment, we analysed several fractions of different household wastes. A maximum of 2.6% of di-(2-ethylhexyl) phthalate (DEHP) was measured in 'compound materials'. More than 90% of all the PAE present in the refuse was due to DEHP. Assuming defined compositions of the refuse we calculated that approx. 1 kg of phthalate esters per ton of dry waste may be codisposed. The actual amount of PAE that could be eluted by the leachate was estimated using laboratory bioreactors which were filled with waste of exactly known composition. Only approx. 1 g of PAE per ton of dry waste was leached. However, the elution of hydrophobic DEHP by the leachate is dependent on the composition of the waste which gave rise to different concentrations of dissolved organic carbon. Because of the experimental setup the amounts of leached PAE represent minimum levels of possible environmental contamination. Hence, there will be a constant output of PAE from unlined municipal landfills for decades.

Environmental Monitoring↗
PubMed1997

[The "pinch off" syndrome: a complication of implantable catheter systems in the subclavian vein].

We report the case of a 63-year-old male patient who received a subcutaneous Port-a-cath system in the right subclavian vein for administration of chemotherapy. Five weeks after successful use, flushing with NaCl 0.9% caused a painless subcutaneous swelling. Fluoroscopy confirmed a leakage below the right clavicle. The catheter was explanted and replaced by a new catheter via Seldinger technique. Two weeks later another leakage occurred and the catheter was removed definitively. Defective equipment was ruled out by the catheter producing company. The "pinch off" syndrome, a rare phenomenon of catheter compression and consecutive catheter fracture, is described, together with the diagnostic signs, the incidence and preventive measures suggested in the literature.

Antineoplastic Agents↗
PubMed1997

Anti-insect toxin 5 (AaIT5) from Androctonus australis.

An insect-selective scorpion toxin (AaIT5) was purified from the venom of the North African scorpion Androctonus australis, and its amino acid sequence was determined by a combination of automated Edman degradation, electrospray-ionization mass spectrometry, and sequence alignment. This insect toxin is very potent against the tobacco budworm, Heliothis virescens (100% lethal dose < 1.8 microg/100 mg body mass) and shows a distinct insect specificity and various symptoms. It is not toxic to mice after subcutaneous injection. The molecular mass of this toxin is 6882 Da and the amino acid sequence is similar to those of Androctonus australis anti-insect toxin 4 (AaIT4), Leiurus quinquestriatus depressant anti-insect toxins (LqhIT2, LqqIT2), and Buthotus judaicus depressant anti-insect toxin (BjIT2).

Amino Acid Sequence↗
PubMed1997

Comparative analysis of the genomes of the bacteria Mycoplasma pneumoniae and Mycoplasma genitalium.

The sequenced genomes of the two closely related bacteria Mycoplasma genitalium and Mycoplasma pneumoniae were compared with emphasis on genome organization and coding capacity. All the 470 proposed open reading frames (ORFs) of the smaller M.genitalium genome (580 kb) were contained in the larger genome (816 kb) of M.pneumoniae. There were some discrepancies in annotation, but inspection of the DNA sequences showed that the corresponding DNA was always present in M. pneumoniae. The two genomes could be subdivided into six segments. The order of orthologous genes was well conserved within individual segments but the order of these segments in both bacteria was different. We explain the different organization of the segments by translocation via homologous recombination. The translocations did not disturb the continuous bidirectional course of transcription in both genomes, starting at the proposed origin of replication. The additional 236 kb in M.pneumoniae,compared with theM.genitalium genome, were coding for 209 proposed ORFs not identified in M.genitalium. Of these ORFs, 110 were specific to M.pneumoniae exhibiting no significant similarity to M.genitalium ORFs, while 76 ORFs were amplifications of ORFs existing mainly as single copies in M. genitalium. In addition, 23 ORFs containing a copy of either one of the three repetitive DNA sequences RepMP2/3, RepMP4 and RepMP5 were annotated in M.pneumoniae but not in M.genitalium,although similar DNA sequences were present. TheM.pneumoniae-specific genes included a restriction-modification system, two transport systems for carbohydrates, the complete set of three genes coding for the arginine dihydrolase pathway and 14 copies of the repetitive DNA sequence RepMP1 which were part of several different translated genes with unknown function.

Base Composition↗
PubMed1997

MTS1 expression and prognosis in acute myeloid leukemia.

MTS1, a tumor suppressor gene located on chromosome 9p21, has been shown to be altered in a number of human tumor cell lines, primary solid tumors, and leukemias. In this study we found low expression of MTS1 in lymphocytes from seven of nine healthy donors, but in none of eight granulocyte samples from the same controls, suggesting a physiological role of MTS1 in peripheral blood cells capable of proliferation, but not in end-stage differentiated cells. We detected MTS1 mRNA expression in 38 of 57 patients (66%) with acute myelogenous leukemia (AML) treated in a standardized clinical protocol. No deletion of the MTS1 gene was found in any of the AML samples tested. There was no significant association between expression of MTS1 and response to therapy, progression-free, or overall survival. Except for a negative correlation between MTS1 level and leukocyte count at diagnosis (p = 0.03), there was also no association with any of the known prognostic parameters in AML. We conclude that MTS1 shows a significantly higher expression in leukemic than in normal peripheral blood cells, that deletion of MTS1 is not a frequent event in AML, and that its expression is not significantly correlated with outcome of the disease.

Cyclin-Dependent Kinase Inhibitor p16↗
PubMed1997

Spatial distribution of beta-spectrin in normal and dystrophic human skeletal muscle.

Spectrin, a major component of the erythrocyte membrane skeleton, has previously been shown to form a two-dimensional lattice in erythrocytes, and in avian or chicken skeletal muscle. Those results were mainly obtained with antibodies against alpha-spectrin. Using immunofluorescence of semithin cryosections and single muscle fiber preparations, we show here that beta-spectrin forms a costameric network which covers the plasma membrane of human skeletal muscle. These spectrin costameres are correlated with the Z-bands. They are longitudinally connected by fine strands and interrupted by myonuclear lacunae. Under mechanical stretching, the costameres retained their correlation to the Z-bands in normal and dystrophin-deficient muscle, up to the point at which the sarcolemma was disrupted. In stretched muscle, in some regions of the stretched fibers in which the costameres seemed to form double strands, the usually 1:1 correlation of spectrin to the Z-bands changed to a 2:1 relation. In dystrophin-deficient muscle, the costameric scaffold of spectrin in the well-preserved fibers appeared normal, indicating that spectrin can be correctly localized in the absence of dystrophin and that the subcellular spectrin organization does not primarily depend on dystrophin expression. The regular organization and the correlation of spectrin costameres to the Z-bands was notable even in stretched Duchenne muscular dystrophy (DMD) muscle. On the other hand, single teased muscle fibers of DMD muscle showed various degrees of morphological alterations of the costameric network, ranging from a focal disarray to complete loss of costameric organization. Because these findings indicate that the costameric spectrin scaffold undergoes secondary changes during the course of the dystrophic process in dystrophin-deficient muscle, spectrin staining of isolated muscle fibers may also serve as a tool to monitor the effect of gene therapy experiments at the single fiber level.

Blotting, Western↗
PubMed1997

The status of p53 in the metastatic progression of colorectal cancer.

In order to investigate the role of TP53 in tumour progression and metastasis, we analysed 33 liver metastases of colorectal carcinomas and 19 primary colon carcinomas from the same hospital with respect to mutational changes, loss of heterozygosity and expression of the TP53 tumour suppressor gene. Direct sequencing of PCR products corresponding to the coding region of TP53 revealed that 13 of 19 primary tumours (68%) and 23 of 33 liver metastases (70%) had mutations in the TP53 gene. The distribution of mutations along the coding region of TP53 was similar in liver metastases compared to primary tumours. Thus, codon specificity did not seem to be a relevant factor and cells carrying specific TP53 mutations seem to have no selective advantage in the metastasising process. Comparing our data with the mutational spectra found in other countries did not reveal differences in the distribution of mutations along the coding region. Most of the metastases analysed showed loss of heterozygosity (LOH, 9 of 12 cases, 75%) and strong nuclear staining in immunohistochemistry (10 of 17 cases, 59%). Furthermore, with respect to mRNA expression levels, tumours carrying TP53 mutations showed significantly higher p53 mRNA levels compared to those without TP53 mutations. Thus, regulation of p53 mRNA levels seems to be subject to selection processes in tumourigenesis.

Chromosome Deletion↗
PubMed1997

Gastrointestinal Tract Cancer Liaison Office: an attempt to organise clinical research in Europe.

The Gastrointestinal Tract Cancer Liaison Office (GITCLO) was developed in an attempt to organise the increasing body of clinical research in gastrointestinal tumours in Europe. This paper represents an analysis, by tumour localisation, of the trials collected for the second edition of the GITCLO booklet. The list of cooperative groups, chairmen and study coordinators is given with their respective telephone and telefax numbers. A total of 84 trials were collected, conducted by 46 co-operative groups in 14 countries. For each organ and stage of disease, a summary of concepts investigated is given with the references of the study co-ordinator. Obviously, too many questions are raised at the same time. In colorectal cancer, for example, a total of 41 trials exploring 22 concepts are currently open for patients' registration. We hope that the present attempt to clarify the situation of clinical research in the field of gastrointestinal cancers in Europe will speed up therapeutic progress in the best interest of the patients.

Colorectal Neoplasms↗
PubMed1997

Changes of laminin beta 2 chain expression in congenital muscular dystrophy.

We studied the distribution of laminin beta 2 chain in the skeletal muscle basement membrane of 16 patients with congenital muscular dystrophy (CMD) by immunohistochemistry. A dramatic reduction in the laminin beta 2 staining was observed in four patients with classical merosin-negative CMD. A moderate reduction of laminin beta 2 labelling was observed in four patients with partial merosin deficiency and two patients with merosin-positive CMD. Two patients with merosin-positive CMD had no apparent changes in the expression of laminin beta 2. In three patients and one fetus diagnosed as Walker-Warburg syndrome (WWS) the laminin beta 2 pattern was similar to normal controls. We conclude that a primary deficiency in the laminin alpha 2 chain may lead to a vast or moderate reduction in the laminin beta 2 chain in the skeletal muscle membrane.

Adolescent↗
PubMed1997

Mobilization of predominantly Philadelphia chromosome-negative blood progenitors using cyclophosphamide and rHUG-CSF in early chronic-phase chronic myeloid leukaemia: correlation with Sokal prognostic index and haematological control.

Mobilization of Philadelphia chromosome (Ph) negative blood progenitors was attempted in 23 newly diagnosed chronic myeloid leukaemia (CML) patients using a regimen of cyclophosphamide (CY) 5 g/m2 and rHUG-CSF 150 microg/m2 daily. This regimen was well tolerated with no major adverse events reported. More than 2 x 10(6)/kg CD34+ cells were collected in 21 patients (91%). Predominantly Ph-negative mobilization (0-25% Ph-positive) was seen in 30% of cases overall and was confined to patients with a Sokal prognostic score < 1 (7/11 with Sokal score <1; 0/12 with Sokal score > or = 1). Within the low Sokal index group, a low WBC count pre-mobilization and a low WBC nadir both correlated strongly with Ph-negative mobilization (P = 0.006 and 0.02 respectively). Five of 19 patients receiving at least 6 months of Roferon A therapy post mobilization achieved a major cytogenetic response; all five patients were Ph-negative mobilizers. Therefore CML patients can be divided into a good-prognosis group in whom predominantly Ph-negative progenitors can be mobilized using a regimen of moderate intensity if haematological control is achieved pre-mobilization, and a poor-prognosis group for whom predominantly Ph-positive cells are mobilized with this regimen regardless of haematological control.

Adult↗
PubMed1997

The KID study IV: effects of inpatient rehabilitation on the frequency of glucose self-monitoring, quality of further primary care, on time being unable to work and on everyday psychic strain of type I and type II diabetics--a one-year follow-up. Kissingen Diabetes Intervention Study.

The Kissingen Diabetes Intervention Study (KID) evaluated 1,050 diabetic patients of the German Federal Insurance Institution for Salaried Employees (BfA) admitted for inpatient rehabilitation in a single-center, prospective, longitudinal study which was carried out to collect data concerning the structure of the patient cohort, socioeconomic factors, psychological data and state of medical care by consecutively registered random tests. These results have already been published. We will now report on the outcome 6 and 12 months after inpatient treatment. Consisting of rather young diabetics in higher professional standing, our patient cohort is especially interesting for health policy. The numbers of type I diabetics and of insulin-treated type II diabetics who self-monitor blood glucose levels several times daily significantly increased after inpatient rehabilitation. This situation is maintained 6 and 12 months after discharge. The number of type II diabetics on diet or oral hypoglycemics who do not monitor urinary glucose levels at all, is significantly reduced. The frequency of daily or weekly checks is significantly raised even after 12 months. Due to inpatient diabetic education, self-monitoring of glucose levels plays a more important role in primary care of these patients. 68.5% of all type I and about 60% of all type II diabetics receive test material without problems and are encouraged to continue monitoring. However, about 30% of type I and type II diabetics under primary-care management are still supplied with test material only when especially demanding it. The frequency of consultations in primary care diabetic management remains unchanged after inpatient treatment. The quality of diabetic management in primary care is improved by patient education. Monitoring of HbA1 is significantly increased in type I diabetics and significantly increased in type II diabetics. A similar development is seen in monitoring urinary albumin excretion but here are still deficits. For type II diabetics, the body weight and serum lipids are increasingly controlled main parameters. But in many places and especially in the case of type II diabetics the fasting glucose level is still used as main parameter. Compared with the 6 months prior to inpatient treatment, times when type I and type II diabetics are unable to work are significantly reduced in the 6 months and 12 months after-wards. Evaluating individual profiles of psychosocial strain shows that the more intense confrontation with problems of the disease and demands of the treatment can lead to a poorer quality of life in several categories. This was seen in the categories anxiety, depression, fear of hypoglycemias in the case of type I diabetics, restriction of leisure time activities, relationship with the partner and acceptance of disease. Only in the categories patient-physician relationship and professional strain was an improvement found. These alterations are still demonstrable after 6 and 12 months.

Absenteeism↗
PubMed1997

Collection and recruitment of CD34+ cells during large-volume leukapheresis.

Although sufficient progenitor cells for hematopoietic rescue following high-dose therapy may be obtained in a single leukapheresis, the majority of patients require multiple procedures. In an attempt to minimize the number of leukapheresis and maximize collection efficiency, we undertook large-volume leukapheresis in 17 patients with a variety of hematologic malignancies. Twenty-four procedures were performed over a 6-h period, with a mean of 21 L of blood processed. By employing a modified collection set, three separate 2-h collection bags were analyzed for a number of variables. CD34+ cells are collected at a steady rate throughout the procedure, with no evidence of exhaustion of progenitor cells. There was evidence of progenitor cell recruitment, with 1.4-fold more CD34+ cells in the collected product than were present in the blood at the beginning of the procedure. Initiation of leukapheresis was based on the blood CD34+ count, and this value was strongly correlated with the number of CD34+ cells in the collected product. The procedure is safe and relatively simple and minimizes the number of leukaphereses required to collect adequate progenitors for autologous transplantation.

Adolescent↗
PubMed1997

Interactions of recombinant and wild-type baculoviruses with classical insecticides and pyrethroid-resistant tobacco budworm (Lepidoptera: Noctuidae).

In tests with neonate Heliothis virescens (F.), we characterized interactions of all combinations of a recombinant Autographa californica (Speyer) nuclear polyhedrosis virus (AcAaIT) that expresses an insect-selective neurotoxin (AaIT) and wild-type AcNPV when combined with low concentrations of several conventional insecticides. All combinations of the recombinant virus AcAaIT and insecticides showed a positive interaction (decrease in the median lethal time (LT50) compared with the LT50 for either component alone). A type II pyrethroid (cypermethrin, which modifies currents of sodium channels) and a carbamate (methomyl, an inhibitor of acetylcholinesterase) were synergistic in combination with AcAaIT. Other insecticides also showed a positive interaction when tested in combination with the recombinant virus, but joint activity was slightly antagonistic (i.e., less than predicted activity when combined) with wild-type AcNPV. We also characterized the effectiveness of AcAaIT against pyrethroid-resistant H. virescens larvae. Our results show that a resistant strain of H. virescens is more sensitive to the recombinant virus compared with a susceptible strain. Results of these studies should be useful in planning of future field trials to increase the effectiveness of nuclear polyhedrosis viruses and to manage resistance to pyrethroids and other insecticides.

Animals↗
PubMed1997

The thioredoxin reductase system of mycoplasmas.

Representative species of the Mollicutes possess a thioredoxin reductase system (NTS) composed of a low-molecular-mass thioredoxin (TRX) and NADPH-binding thioredoxin reductase (NTR). The TRXs of Mycoplasma pneumoniae and M. capricolum have molecular masses of 11-2 and 12 kDa, respectively, and are stable at 90 degree C for 10 min. Both TRXs reacted with monospecific polyclonal antibodies generated against the Bacillus subtilis TRX, but not with anti-Escherichia coli TRX antisera. The M. capricolum and M. pneumoniae NTRs were partially purified and were found to be active with the homologous TRX, but not with the TRX of B. subtilis or E. coli. The NTS activity had an optimal pH of 6.5-7.5 and was dependent on NADPH as an election donor, a requirement which could not be fulfilled by NADH. The genes encoding the TRX and NTR (trxA and trxB) or M. pneumoniae were cloned and sequenced. The comparative analysis of the predicted amino acid sequence of trxA showed that the 11.2 kDa protein (102 aa) shared 26-68% sequence similarity with products of other known trxA genes and contained the conserved active site Cys-Gly-Pro-Cys. The predicted amino acid sequence of trxB contained 315 residues with a conserved NADPH binding domain and FAD binding domains I and II. The cysteine dithiol redox active region had isoleucine rather than threonine at the active site, as compared with other NTRs. The high activity of the NTS in mycoplasmas suggests that mycoplasmas may have evolved the NTS to protect themselves from the consequences of their self-generated oxidative challenge.

Amino Acid Sequence↗
PubMed1997

Transposon mutagenesis reinforces the correlation between Mycoplasma pneumoniae cytoskeletal protein HMW2 and cytadherence.

A new genetic locus associated with Mycoplasma pneumoniae cytadherence was previously identified by transposon mutagenesis with Tn4001. This locus maps approximately 160 kbp from the genes encoding cytadherence-associated proteins HMW1 and HMW3, and yet insertions therein result in loss of these proteins and a hemadsorption-negative (HA-) phenotype, prompting the designation cytadherence-regulatory locus (crl). In the current study, passage of transformants in the absence of antibiotic selection resulted in loss of the transposon, a wild-type protein profile, and a HA+ phenotype, underscoring the correlation between crl and M. pneumoniae cytadherence. Nucleotide sequence analysis of crl revealed open reading frames (ORFs) orfp65, orfp216, orfp41, and orfp24, arranged in tandem and flanked by a promoter-like and a terminator-like sequence, suggesting a single transcriptional unit, the P65 operon. The 5' end of orfp65 mRNA was mapped by primer extension, and a likely promoter was identified just upstream. The product of each ORF was identified by using antisera prepared against fusion proteins. The previously characterized surface protein P65 is encoded by orfp65, while the 190,000 Mr cytadherence-associated protein HMW2 is a product of orfp216. Proteins with sizes of 47,000 and 41,000 Mr and unknown function were identified for orfp41 and orfp24, respectively. Structural analyses of HMW2 predict a periodicity highly characteristic of a coiled-coil conformation and five leucine zipper motifs, indicating that HMW2 probably forms dimers in vivo, which is consistent with a structural role in cytadherence. Each transposon insertion mapped to orfp216 but affected the levels of all products of the P65 operon. HMW2 is thought to form a disulfide-linked dimer, formerly designated HMW5, and examination of an hmw2 deletion mutant confirms that HMW5 is a product of the hmw2 gene.

Bacterial Adhesion↗
PubMed1997

Topoisomerase II alpha mRNA and tumour cell proliferation in non-Hodgkin's lymphoma.

AIMS: To elucidate potential mechanisms of drug resistance, levels of topoisomerase II alpha mRNA, a target for cytostatic drugs, were measured in cryopreserved tumour tissue from 36 patients with non-Hodgkin's lymphoma. To evaluate the potential association between topoisomerase II alpha and cell proliferation, Ki-67 immunostaining was also assessed. METHODS: The study population comprised 13 patients with low grade and 20 with high grade non-Hodgkin's lymphoma. Three patients had recurrent disease. Topoisomerase II alpha mRNA was quantitated by using reverse transcription polymerase chain reaction (RT-PCR) and the PCR product measured by using HPLC. The MIB-1 monoclonal antibody was used for Ki-67 immunostaining. RESULTS: Levels of topoisomerase II alpha mRNA correlated strongly with the Ki-67 labelling index and were higher in high grade than in low grade lymphomas. Patients in complete clinical remission of high grade lymphoma had a higher Ki-67 labelling index and tended to have higher topoisomerase II alpha mRNA levels. CONCLUSIONS: Although topoisomerase II alpha mRNA levels may be indicative of sensitivity to drugs, it is more likely that they reflect the proliferation status of the cell, which in turn involves a large number of additional molecular systems that influence response to treatment.

Adolescent↗