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Biomedical subjects

J Meier

Publications and source records attributed to J Meier.

At least 55 records · Page 3Linked to original sources
PubMed1998

Promoter structures and differential responses to viral and nonviral inducers of chicken type I interferon genes.

Two serologically distinct type I interferons (IFNs), designated ChIFN1 and ChIFN2, are known in the chicken. ChIFN1 is encoded by a family of 10 or more genes, whereas ChIFN2 is encoded by a single gene. We show here that ChIFN1 and ChIFN2 transcripts are both strongly induced by Newcastle disease virus in primary chicken macrophages. By contrast, oral administration of the imidazoquinoline S-28463, which selectively induces IFN-alpha in mammals, led to a rapid accumulation of ChIFN1 (but not ChIFN2) transcripts in adult chicken spleen and thymus. The 5'-upstream region of the ChIFN2 gene contains a NF-kappaB consensus motif flanked by a sequence element that could serve as a binding site for transcription factor IRF-1, reminiscent of mammalian IFN-beta promoters, and it mediated powerful virus inducibility in a duck fibroblast cell line when cloned in front of a promoterless luciferase reporter gene. The 5'-upstream region of the cloned ChIFN1 gene contains two putative binding sites for IRF-1, but lacks NF-kappaB-binding sites, and it did not respond well to virus in transfected cells. Thus, the promoters of ChIFN1 and ChIFN2 genes not only exhibited differential responses to nonviral inducers in vivo, but also differed in structure and response to virus in transfected cells. These findings indicate that ChIFN2 represents the avian homolog of mammalian IFN-beta, whereas ChIFN1 seems to correspond to mammalian IFN-alpha.

Animals↗
PubMed1998

Pharmacologic treatment of hypertension in the Department of Veterans Affairs during 1995 and 1996.

Patterns of antihypertensive drug use, the cost of this care and potential savings with changes of treatment patterns, were studied for all hypertensives treated at US Veterans Affairs (VA) medical facilities for fiscal years 1995 and 1996. Data was aggregated by individual medication as well as by antihypertensive drug class. Cost estimates were based on median cost and number of units for each dosage form of each medication dispensed at all facilities. Potential savings were estimated by substituting beta-blockers or diuretics for calcium antagonists. In a subset of patients the prevalence of hypertension, and among hypertensives the prevalence of coronary artery disease, congestive heart failure, and diabetes mellitus, was determined. For these patients, patterns of treatment by antihypertensive drug class was examined. For all VA facilities, of the 10 most frequently prescribed antihypertensives in 1995, four were calcium antagonists, two angiotensin converting enzyme (ACE) inhibitors, two beta-blockers, and two diuretics. In 1996, this was changed by the addition of an ACE inhibitor and the subtraction of a diuretic combination. Calcium antagonists accounted for 37% of treatment days in 1995 and 35% in 1996, ACE inhibitor use went from 34% to 36%, beta-blockers from 17% to 18%, and diuretic use remained at 12%. In 1996, approximately 86.6 million dollars were spent on calcium antagonists, 51.8 million on ACE inhibitors, 7.9 million on beta-blockers, and 3.6 million on diuretics. The estimated annual cost savings for each 1% conversion of calcium antagonists to beta-blockers would be $713,000 and to diuretics $758,000. In a subset of 7526 hypertensive patients with known comorbid conditions, calcium antagonists and ACE inhibitors were also the most commonly used drug classes for all categories of patients, including those without coronary artery disease, congestive heart failure, and diabetes mellitus. Calcium antagonists and ACE inhibitors were the most commonly dispensed antihypertensives at VA facilities for both 1995 and 1996, with a small decrease in calcium antagonist use from 1995 to 1996. The cost implications of these practice patterns as compared with the primary use of diuretics and beta-blockers are enormous.

Adrenergic beta-Antagonists↗
PubMed1998

Transgenic mice in the study of ALS: the role of neurofilaments.

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurological disorder of multiple etiologies that affects primarily motor neurons in the brain and spinal cord. Abnormal accumulations of neurofilaments (NFs) in motor neurons and a down-regulation of mRNA for the NF light subunit (NF-L) are associated with ALS, but it remains unclear to what extent these NF perturbations contribute to human disease. Transgenic mouse studies demonstrated that overexpression of normal and mutant NF proteins can sometimes provoke a motor neuronopathy characterized by the presence of abnormal NF accumulations resembling those found in ALS. Remarkably, the motor neuronopathy in transgenic mice overexpressing human NF heavy (NF-H) subunits was rescued by the co-expression of a human NF-L transgene at levels that restored a correct stoichiometry of NF-L to NF-H subunits. Transgenic approaches have also been used to investigate the role of NFs in disease caused by Cu/Zn superoxide dismutase (SOD1) mutations, which is responsible for approximately 2% cases of ALS. Studies with transgenic mice expressing low levels of a fusion NF-H/lacZ protein, in which NFs are withheld from the axonal compartment, suggested that axonal NFs are not toxic intermediates required for SOD1-mediated disease. On the contrary, overexpression of human NF-H proteins was found to confer an effective protection against mutant SOD1 toxicity in transgenic mice, a phenomenon that may be due to the ability of NF proteins to chelate calcium. In conclusion, transgenic studies showed that disorganized NFs can sometimes have noxious effects resulting in neuronopathy. However, in the context of motor neuron disease caused by mutant SOD1, there is emerging evidence that NF proteins rather play a protective role.

Amyotrophic Lateral Sclerosis↗
PubMed1997

Mitotic phosphorylation of the lamin B receptor by a serine/arginine kinase and p34(cdc2).

The lamin B receptor (LBR) is an integral protein of the inner nuclear membrane that is modified at interphase by a nuclear envelope-bound protein kinase. This enzyme (RS kinase) specifically phosphorylates arginine-serine dipeptide motifs located at the NH2-terminal domain of LBR and regulates its interactions with other nuclear envelope proteins. To compare the phosphorylation state of LBR during interphase and mitosis, we performed phosphopeptide mapping of in vitro and in vivo 32P-labeled LBR and analyzed a series of recombinant proteins and synthetic peptides. Our results show that LBR undergoes two types of mitotic phosphorylation mediated by the RS and the p34(cdc2) protein kinases, respectively. The RS kinase modifies similar sites at interphase and mitosis (i.e. Ser76, Ser78, Ser80, Ser82, Ser84), whereas p34(cdc2) mainly phosphorylates Ser71. These findings clarify the phosphorylation state of LBR during the cell cycle and provide new information for understanding the mechanisms responsible for nuclear envelope assembly and disassembly.

Amino Acid Sequence↗
PubMed1997

[Social medicine in the ecology curriculum--Leipzig experiences with a social medicine practicum].

Apart from only offering lectures, Leipzig university introduced, within the scope of the "Ecological course", a newly outlined practical training in the field of social medicine. The topics of this practical training were: living with handicaps: chronic illness; psychosocial problems. The training consisted of two seminars and one attendance at disabled persons' unions and self-help groups. In addition to that, extern experts held lectures on the feasibility of rehabilitation. Each team, consisting of 3-5 students, was expected to write a report on their attendance in order to prove their efforts. Later on, these reports suppled the basis for discussion in the second seminar. The high quality of these reports clearly shows the students' interest in this kind of training. Some especially interested students took an active part in a final scientific colloquium, delivering their own lecture reports. Summing up, this teaching concept proved truly successful and should be continued.

Adult↗
PubMed1996

The lamin B receptor (LBR) provides essential chromatin docking sites at the nuclear envelope.

Morphological studies have established that peripheral heterochromatin is closely associated with the nuclear envelope. The tight coupling of the two structures has been attributed to nuclear lamins and lamin-associated proteins; however, it remains to be determined which of these elements are essential and which play an auxiliary role in nuclear envelope-chromatin interactions. To address this question, we have used as a model system in vitro reconstituted vesicles assembled from octyl glucoside-solubilized nuclear envelopes. Comparing the chromosome binding properties of normal, immunodepleted and chemically extracted vesicles, we have arrived at the conclusion that the principal chromatin anchorage site at the nuclear envelope is the lamin B receptor (LBR), a ubiquitous integral protein of the inner nuclear membrane. Consistent with this interpretation, purified LBR binds directly to chromatin fragments and decorates the surface of chromosomes in a distinctive banding pattern.

Animals↗
PubMed1996

Nerve growth factors from snake venoms: chemical properties, mode of action and biological significance.

An overview of nerve growth factors (NGF) and their receptor system is presented. This general introduction deals with mouse and human NGF, since most of the fundamental knowledge is based on these mammalian proteins. Great emphasis is laid on the nonneuronal NGF effects which are well discussed for their possible toxinological function. The snake venom NGFs were reviewed with respect to their purification, classification and properties. From the date of their discovery about 40 years ago, researchers have been interested in the possible function of mouse salivary and snake venom NGFs. The physiological relevance of snake venom NGF is therefore widely discussed on the base of experimental facts and hypothetical considerations.

Animals↗
PubMed1996

A novel peptidoglycan-linked lipoprotein (ComL) that functions in natural transformation competence of Neisseria gonorrhoeae.

A novel peptidoglycan-linked lipoprotein (ComL) has been identified which is required for efficient transformation of Neisseria gonorrhoeae by species-related DNA. Although most mutations in comL appear to be lethal, transposon shuttle mutagenesis was successful in generating a single viable comL mutant of N. gonorrhoeae strain MS11. This mutant, N457, exhibits a cratered and crinkled colony morphology and grows slower than wild-type MS11. However, as indicated by electron microscopy, this retardation is due to a small bacterial size rather than to a decreased generation time of the mutant bacteria. Complementation of N457 with an intact comL gene via the Hermes shuttle system fully reconstitutes bacterial size, colony morphology, and transformation competence of the wild-type strain. comL is a single-copy gene and maps downstream of the previously described comA gene. It is transcribed in the opposite direction, probably using the same transcriptional terminator. ComL has a predicted size of 29 kDa and is synthesized in Escherichia coli under the control of its native promoter, which is highly conserved with the E. coli promoter consensus sequence. The 5' end of the coding sequence reveals a lipoprotein secretion signal shown to be functional by gene fusion with alkaline phosphatase (phoA'). In E. coli, cloned ComL can be labelled with [3H]-palmitic acid, thus demonstrating its lipoproteinaceous nature. Palmitoylated ComL appears to be covalently bound to the murein sacculus of E. coli and N. gonorrhoeae since it resists boiling in 4% sodium dodecyl sulphate and is released only by lysozyme treatment. Homologous counterparts of the comL gene are found in Neisseria meningitidis as well as in several nonpathogenic Neisseria species.

Amino Acid Sequence↗
PubMed1996

[Costs-proceeds calculation for radiotherapy; comment].

BACKGROUND: The Health Care Structure Bill (Gesundheitsstrukturgesetz) and the Federal Health Care Tariff Regulation (Bundespflegesatzverordnung) pose new challenges for the chief physician in charge, which he has to face on account of hospital management control with department-specific internal budgeting of services, expenditure and remittance. In view of the impending establishment of care-related lump sums (Fallpauschalen) and special allowances for radiation therapy (Sonderentgelte) as well as the introduction of an appropriate internal budget plan, we resolved to draw up the service-cost ratio for 11 tumor entities, implementing calculation based on process evaluation, and to match this calculation to the actual proceeds from outpatient treatment covered either by general health insurance or private care insurance. MATERIAL AND METHODS: The following 11 tumors were included in the analysis: Glioblastoma multiforme, squamous cell carcinoma of the head and neck, lung cancer, oesophageal cancer, breast cancer, rectal and prostate cancer, cancer of the anal canal and the uterine cervix, Hodgkin's disease and bone metastases. For the description of the services rendered and for the calculation of actual cost, the complex treatment regime was divided into the following steps: administration, medical radiation planning, radiation planning by physicist, workmanship, radiotherapy treatment and medical service. The calculation of costs was made either in- or excluding the cost of teatment facilities and basic investment. The proceeds were calculated according to the regulations of the EBM (dated 1. 10. 1994) for general health insurance patients (median point value 9.35 DPF) and the GOA (dated 1. 7. 1988) for private patients (point value 11 DPF). RESULTS: 1. Calculation by EBM standards: Excluding the cost of facilities and basic investment, there is a profit margin for the following tumor entities amounting to +1.6% (103.18 DM) for ENT tumors, +9.2% (671.90 DM) for carcinoma of the anal canal and +35.8% (1637.84 DM) for bone metastases. All other tumor entities cannot be treated cost-effectively. With the exception of glioblastoma, median loss comes to -20% (-14% to -27.4%, i.e. -809.48 to -1812.84 DM). Including in the calculation the cost of the facilities and investment, only bone metastases can be treated with a profit margin. For all other tumors, the mean loss amounts to -33% (-14.1% to -44.7%) or else -1308.26 to -4550.51 DM. 2. Calculation by GOA standards: Comparing cost and actual proceeds, there is a loss for all tumor entities. Excluding the cost of treatment facilities and investment, median loss amounts to -44% (-33.3% to -53.5%, or -1752.64 DM to -3488.18 DM), including both, mean loss comes to -56% (-47.8% to -53.3% or -3156.33 DM to -6332.43 DM). 3. Calculation of comprehensive cost and of the proceeds: For our own department, considering the cost-proceeds ratio for 1994, we ran up a deficit of 673,767.10 DM for outpatient care. This deficit can mainly be traced back to non-operational hours of the linear accelerator due to machine impairment, maintenance and dosimetric measurements by the physicists, leading to the loss of 53 work-days (14 hours each) amounting to 498,771.34 DM plus general costs of 271,000 DM added to the bill by hospital administration. CONCLUSIONS: As to the reviewed tumor entities, modern standard radiotherapy cannot be administrated cost-effectively. A considerable degree of under-funding is especially evident with the inclusion of cost of investment and of the facilities. The cost-proceeds ratio is most unsatisfactory as regards GOA calculation, which is obsolete as far as service description and service payment is concerned. As it in no way measures up to the required standard of modern radiotherapy, reform is therefore urgently needed.

Costs and Cost Analysis↗
PubMed1995

Purification and characterization of three alpha 2-antiplasmin and alpha 2-macroglobulin inactivating enzymes from the venom of the Mexican west coast rattlesnake (Crotalus basiliscus).

Three distinct alpha 2PI (alpha 2-antiplasmin) degrading and alpha 2M (alpha 2-macroglobulin) inhibiting enzymes, named proteinase a, b and c, have been purified from the venom of Crotalus basiliscus (the Mexican west coast rattlesnake) by fast protein liquid chromatography (anion-exchange chromatography and gel filtration chromatography). SDS-PAGE revealed that proteinase a and b had similar mol. wts (approximately 23,500), whereas proteinase c displayed a mol.wt of approximately 24,200. Their isoelectric points were found to be acidic, ranging from pH 4.8 to 5.7. The proteinase activity of all three enzymes was inhibited in the presence of EDTA. Dependent on enzyme concentration, a progressive and catalytic inactivation of alpha 2PI was induced, leading to an almost complete loss of the plasmin inhibitory activity at a molar ratio of enzyme: alpha 2PI = 0.1 within 60 min. The ability of alpha 2M to protect the esterolytic activity of trypsin from inhibition by soybean trypsin inhibitor was only reduced at a molar ratio of enzyme: alpha 2M = 0.5, whereas no inactivation could be observed when the three venom proteinases were incubated with an excess of alpha 2M, suggesting that the inactivation occurred by complex formation but not by degradation of the intact alpha 2M molecule. In SDS-PAGE, inactivation of human alpha 2PI (mol. wt 68,000) correlated with the appearance of two cleavage products with an approximate mol. wt of 56,000 and 11,000, respectively. The three proteinases had no thrombin-like activity. Plasminogen and factor X were not activated and no platelet aggregation was induced. They degraded the A alpha- and B beta-chain of fibrinogen and showed plasma extravasation-inducing activity following intradermal injection into the abdominal skin. None of the enzymes showed any activity against a series of chromogenic p-nitroanilide substrates.

Animals↗
PubMed1995

Nerve growth factor from the venom of the Chinese cobra Naja naja atra: purification and description of non-neuronal activities.

Nerve growth factor (NGF) was separated from crude Naja naja atra venom by using weak cation-exchange chromatography, followed by reversed-phase liquid chromatography. The yield of the purification was 0.2-0.5% (w/w). The mol. wt was determined to be 13,600 and the protein still induced the typical fibre outgrowth of cultured PC-12 cells in a concentration range of 5-10 ng/ml. Beside this neuronal effect we demonstrated non-neuronal effects of cobra venom NGF, such as induction of plasma extravasation and histamine release from whole blood cells. With human leucocyte preparations, including enriched basophils, there was an increase in C5a-induced histamine release, whereas NGF alone was inactive. Cobra NGF was one-tenth as potent as human recombinant NGF, with a half-maximal stimulation occurring at 10 ng/ml. Cobra NGF and human recombinant NGF showed a modulatory effect on histamine release comparable to the haematopoietic growth factor IL-3. Thus, the non-neuronal effects of cobra NGF may account for immunomodulatory activities during inflammatory events.

Animals↗