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Biomedical subjects

M Roth

Publications and source records attributed to M Roth.

At least 145 records · Page 8Linked to original sources

Recombinant hirudin and front-loaded alteplase in acute myocardial infarction: final results of a pilot study. HIT-I (hirudin for the improvement of thrombolysis).

Recombinant hirudin, a specific thrombin inhibitor, has been shown to accelerate thrombolysis and reduce reocclusions in experimental models. In a pilot trial recombinant hirudin (HBW 023) was used as an adjunctive therapy to thrombolysis with front-loaded tissue plasminogen activator (t-PA) (100 mg.90 min-1) in 40 patients with acute myocardial infarction whose duration of symptoms was less than 6 h. Patients received a bolus of r-hirudin of 0.07 mg.kg-1 b.w. followed by an infusion of 0.05 mg.kg-1.h-1 over 48 h. Complete patency (TIMI grade 3) of the infarct-related artery at 30, 60 and 90 min after the start of thrombolytic therapy was seen in 38.5%, 64.1% and 71.0% of patients, respectively. After 24-48 h, 80% of patients had a complete patent infarct vessel. A very early, complete and sustained patency (TIMI grade 3 at 60 and 90 min and at 24-48 h) was observed in 55% of patients. Reocclusions during the hirudin therapy appeared in six (16.1%) patients, two of whom had a PTCA at 90 min. The only reinfarction was seen after 6 h; this was successfully treated with additional thrombolysis. Major bleedings, mostly related to the invasive procedure, were observed in three patients. Spontaneous organ bleedings and intracerebral haemorrhages did not occur. There was one in-hospital death due to a late retroperitoneal bleeding. In was concluded that, with regard to safety and efficacy, the general feasibility of r-hirudin as adjunctive therapy to thrombolysis with front-loaded t-PA, has been demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Absence of abnormal hyperphosphorylation of tau in intracellular tangles in Alzheimer's disease.

Adult human nerve cells contain tau protein, a phosphorylated microtubule-associated protein, that is hyperphosphorylated in the fetus and in patients with Alzheimer's disease. Hyperphosphorylation, which diminishes the microtubule-binding capacity of tau, destabilizes microtubules and may enhance the formation of paired helical filaments that constitute neurofibrillary tangles in Alzheimer's disease. Here, we use phosphorylation-dependent anti-tau antibodies to detect specific epitopes that characterize hyperphosphorylated tau. Our demonstration of intracellular tangles containing full-length tau that are not immunolabeled by these antibodies suggests that hyperphosphorylation of tau is not obligatory in the formation of neurofibrillary tangles in Alzheimer's disease.

Aged↗

Long-term follow-up after a drug trial for panic disorder.

BACKGROUND: This study investigates the naturalistic course of panic disorder over four years and attempts to identify predictors for outcome. METHOD: 423 DSM-III-R panic disorder patients who had taken part in an international multicentre drug trial were selected for follow-up; we were able to re-interview 367 (87%). For panic attacks, phobic avoidance and disabilities the same rating scales were administered as had been used for the clinical trials. RESULTS: While 61% of all patients experienced at least occasional panic attacks at follow-up, few suffered from serious phobic avoidance (16.7%) or serious disabilities (work 7.9%); family 8.7%; social 13.9%). Panic attack frequency at baseline, original trial medication and continuous use of psychotropic medication during follow-up are not related to outcome, whereas longer duration of illness and more severe phobic avoidance at baseline are unfavourable. CONCLUSION: The course of panic disorder is not uniform. Since long duration of illness and severe phobic avoidance at baseline are predictors for an unfavourable outcome, more rigorous efforts should be undertaken to detect and treat panic disorder at an early stage.

Adolescent↗

Advantages and disadvantages of three-dimensional computed tomography intraoperative localization for functional endoscopic sinus surgery.

Intraoperative three-dimensional computed tomography (3-D-CT) localization has been available for use during functional endoscopic sinus surgery (FESS) for several years, although relatively few otolaryngologists operate in conjunction with this technology. Proponents of intraoperative localization believe that operating with stereotaxis enhances surgical precision and reduces complications. A 1-year review was conducted at the University of Pennsylvania from January 1994 through January 1995. During this period 5% of sinus operations were performed in conjunction with intraoperative localization. The advantages and disadvantages of using intraoperative localization were evaluated for each case. Also examined were type and indication for surgery, anesthesia used, added time, and cost. Overall, intraoperative localization was found to be helpful when anatomy was distorted or obscured. However, selecting patients who may have benefited from localization was often not possible using preoperative data. Ideally, localization should be available for all FESS. Criteria are outlined which will need to be met prior to localization becoming a significant aspect of FESS.

Adult↗

Treatment of active Crohn's ileocolitis with oral pH-modified budesonide. Germany Budesonide Study Group.

Budesonide is a topical steroid which after intestinal absorption is rapidly degraded into inactive metabolites in the liver. Its systemic bioavailability is only 10-15%. In the present open trial the efficiency and safety of oral pH-modified release budesonide were assessed in patients with active Crohn's ileocolitis. This report describes the results of the first 30 of 78 patients. After 6 weeks of treatment with 3 x 3 mg budesonide/day 67% of the patients were in clinical remission. Typical steroid-related side effects were observed in only one patient. Budesonide therefore seems to be suited as an alternative for classical steroids in patients with Crohn's ileocolitis. Its clinical efficacy is comparable with classical steroids but it's rate of steroid-related side effects is lower.

Administration, Oral↗

Crystal structure of the ferredoxin I from Desulfovibrio africanus at 2.3 A resolution.

The crystal structure of the ferredoxin I from the sulfate-reducing bacterium Desulfovibrio africanus (DaFdI) has been solved and refined by X-ray diffraction. The crystals are orthorhombic with a = 96.6 A, b = 58.1 A, and c = 20.7 A, space group P2(1)2(1)2, and two ferredoxin molecules per asymmetric unit. The initial electron density map has been obtained by combining phasing by molecular replacement methods, anomalous scattering, and noncrystallographic averaging. The final crystallographic R factor is 0.182 with 10-2.3 A resolution data. In parallel, the amino acid sequence was redetermined. This showed that DaFdI contains 64 residues (instead of 61) including one free cysteine, one histidine, and one tryptophan in the C-terminal part of the molecule. The current molecular model includes the two molecules of the asymmetric unit, 67 water molecules, and one sulfate ion. The DaFdI overall folding very closely resembles that of ferredoxins of known structure. Comparisons with the single cluster ferredoxins from Desulfovibrio gigas and Bacillus thermoproteolyticus show that the presence or the absence of a disulfide bridge does not significantly affect the folding of the other half of the molecule, including the characteristic alpha-helix of the single cluster ferreddoxins. Like other ferredoxins or analogs, the [4Fe-4S] iron--sulfur cluster presents, at 2.3 A resolution, a cubane-like geometry. By contrast, its immediate environment is different as it includes, besides the four cysteic sulfur ligands, the sulfur atom of the free cysteine. This sulfur atom, which is buried within the protein, is in van der Waals contact with one labile sulfur of the cluster and one liganded cysteic sulfur. The association of a [4Fe-4S] cluster with one free cysteic sulfur is similar to that previously found in both X-ray structures of Azotobacter vinelandii and Peptococcus aerogenes [Stout, C. D. (1989) J. Mol. Biol. 205, 545-555; Backes, G., et al. (1991) J. Am. Chem. Soc. 113, 2055-2064]. Chemical sequence analysis suggests that this characteristic [4Fe-4S] cluster sulfur environment is widely distributed among ferredoxins.

Amino Acid Sequence↗

Presence of axonal paired helical filament-tau in Alzheimer's disease: submicroscopic localization.

While normal adult tau protein is found typically in axons, paired helical filament (PHF) tau has been shown immunohistochemically to be in the somatodendritic compartment in Alzheimer's disease (AD). The small amount of PHF-tau (8-11%) found in white matter with immunochemical methods is shown here by immunoelectron microscopy to be located in axons. It is localized to straight filament variants of PHFs. The small amount of PHF-tau in white matter, therefore, appears not to result from the contamination of immunochemical preparations but to be an integral constituent of affected axons in AD.

Alzheimer Disease↗

DNA topoisomerases from Streptomyces noursei: influence of coumarins and quinolones on the enzymic activity.

DNA topoisomerases have been purified from Streptomyces noursei. DNA gyrase and topoisomerase I show a differential sensitivity against quinolones and coumarins compared to the E. coli enzymes. Streptomyces gyrase is resistant to much higher levels of various drugs than is the E. coli enzyme. The observed differences between the gyrases from streptomycetes and E. coli are discussed in the light of present literature data.

Coumarins↗

A granulocyte inhibitory protein overexpressed in chronic renal disease regulates expression of interleukin 6 and interleukin 8.

Growing evidence suggests that cytokine expression is influenced by locally produced mediators, thus modifying the pluripotential effects of cytokines toward a tissue-specific inflammatory reaction. The granulocyte inhibitory protein (GIP), a 23-kDa protein found to be significantly overexpressed in patients with chronic renal failure, increases autocrine transcription and expression of interleukin (IL) 6 and IL-8 in human mesangial cells. Moreover, GIP alone induced the transcription of c-jun mRNA; however, in combination with IL-6, it stimulated de novo synthesis of DNA and the transcription of both c-jun and c-fos genes. The data suggest that the overall effect of GIP results in the modulation of the glomerular response to injury and contributes to the progression of glomerulosclerosis.

Cells, Cultured↗

The vascular nervous skeleton: a disregarded factor of vascular pathology.

The nervous supply of the vascular wall in its organ entirety represents the felt-like 'nervous skeleton'. Its growth is more vulnerable than that of any other tissue component of the developing vessel wall. Selective growth impairment of the vascular nervous skeleton should result in developmental vascular stenosis. Escape of the epithelial or smooth muscle cells from the confines of the nervous skeleton should be taken into account as a possible common denominator of carcinogenesis and atherogenesis.

Arteriosclerosis↗

Procoagulant activity of PPD-stimulated human lymphocytes after cryopreservation.

OBJECTIVE: Human mononuclear cells from a previously sensitized donor generate procoagulant activity (PCA) following stimulation with purified protein derivative (PPD). Lymphocytes of tuberculous pleural effusions are also highly responsive to PPD stimulation. We examined the influence of cryopreservation on lymphocytes following stimulation with PPD. DESIGN: Peripheral blood lymphocytes of 5 healthy PPD skin test positive subjects were incubated with either PPD, thromboplastin, or concanavalin A (Con A) at concentrations of 0, 1, and 10 micrograms/ml. PCA was determined by measuring the recalcification time. Tests were repeated following cryopreservation for 4 weeks. RESULTS: Incubation of fresh lymphocytes led to a dose dependent shortening of recalcification time: PPD (0-1-10 micrograms/ml: 100-84-65%), thromboplastin (0-1-10 micrograms/ml: 100-85-62%), and Con A (0-1-10 micrograms/ml: 100-85-42%). These results were highly reproducible when tests were repeated 6 weeks later. Cryopreservation did not significantly affect the expression of PCA following incubation with PPD and with thromboplastin. In contrast, cryopreservation significantly diminished the degree of Con A generated PCA. CONCLUSION: Cryopreservation and storage of human lymphocytes is possible without alteration of PCA expression following their incubation with PPD or thromboplastin.

Blood Coagulation Factors↗

Metacarpophalangeal joint implant arthroplasty.

Rheumatoid arthritis (RA) usually requires lifelong treatment and sometimes surgery. Metacarpophalangeal joint (MCPJ) implant arthroplasty is one surgical treatment for patients with severe RA malformation of the finger joints. Although not a cure, MCPJ implant arthroplasty can enhance patients' quality of life by improving their performance of independent activities of daily living. The silicone implant acts as a spacer until tendons and connective tissues are able to control the joint's functions. Comprehensive preoperative and postoperative patient teaching and aggressive physical therapy are needed to achieve optimal outcomes in patients who undergo this surgical procedure.

Arthritis, Rheumatoid↗

Immunohistochemical staging of neurofibrillary degeneration in Alzheimer's disease.

Antibodies to different phosphorylated and non-phosphorylated tau epitopes have been used to identify three histologically distinct types of neurofibrillary tangles in Alzheimer's disease. Intracellular tangles (Type 1) were identified by antibodies recognizing epitopes throughout the tau molecule, including the NH2-terminus. Compact extracellular tangles (Type 2) were characterized by the loss of NH2-terminal immunoreactivity and retention of other tau epitopes. Dispersed extracellular tangles (Type 3) were characterized by the presence of epitopes associated with the microtubule binding region and the COOH-terminus. These three types of tangles, found in situ in hippocampus, could be created experimentally by proteolytic treatment of brain sections. These findings suggest that three stages of neurofibrillary degeneration can be understood as a sequential stripping of paired helical filaments in which the loss of amino-terminus epitopes, followed by loss of phosphorylated epitopes, results in the appearance of dispersed extracellular tangles containing PHF-core epitopes.

Alzheimer Disease↗

Influence of digoxin-like immunoreactive factor on late complications in patients with diabetes mellitus.

The aim of this study was to compare the intensity of typical late complications in diabetic patients (n = 65, 28 type I, 37 type II) who were not on glycoside drugs with low vs. high serum levels of digoxin-like immunoreactive factor (DLIF: group I, n = 42, DLIF < or = the detection limit of 0.2 ng ml-1; and group II, n = 23, mean +/- SEM: 1.17 +/- 0.31 [0.25-4.96] ng ml-1). For detection of nephropathy, urinary albumin excretion (24 h) and creatinine clearance tests were used. For coronary heart disease a questionnaire and standard ECG; for peripheral occlusive vascular disease a questionnaire; for eye disease a fundoscopy; for neuropathy a neurological score system; and for autonomic neuropathy a standardized test battery was employed. Patients with high DLIF levels showed better test results in vibratory perception (95.7 +/- 1.5 vs. 82.8 +/- 3.8%, normal finding = 100%, 2p = 0.016), had better percentile localizations concerning maximal pupillary area in darkness (28.4 +/- 6.6 vs. 8.1 +/- 1.8%, 2p = 0.0004), contraction velocity at 1 s (21.5 +/- 5.8 vs. 8.0 +/- 2.2%, 2p = 0.012), and dilation velocity at 6 s (23.0 +/- 6.8 vs. 10.5 +/- 2.5%, 2p = 0.041), had less retinopathy (with retinopathy: 26.1% vs. 64.3%, 2p = 0.0028), and better percentile localizations in the respiratory sinus arrhythmia test (68.4 +/- 7.3 vs. 44.1 +/- 4.9%, 2p = 0.0064). There was no difference concerning nephropathy, blood pressure, coronary heart disease and peripheral vascular disease. Separate analysis according to the type of diabetes confirmed the results in each group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Characterization of angiotensin II receptors in cultured adult rat cardiac fibroblasts. Coupling to signaling systems and gene expression.

Cardiac hypertrophy is largely due to cardiac fibroblast growth and increased synthesis of extracellular matrix. This study has investigated the contribution of the vasoactive hormone, angiotensin II, toward this hypertrophic process. We have demonstrated that cultures of adult rat cardiac fibroblasts express AT1 but not AT2 receptors for angiotensin II. The ability of angiotensin II to stimulate phosphoinositide catabolism and to elevate intracellular calcium concentrations in these cells was blocked by losartan, a specific AT1 receptor antagonist, but not by the AT2 receptor antagonist CGP 42112. Exposure of adult cardiac fibroblasts to angiotensin II resulted in the induction of several growth-related metabolic events including c-fos protooncogene expression and increased synthesis of DNA, RNA, and protein. Angiotensin II was also found to induce collagen type I, alpha 1 chain transcript expression in cardiac fibroblasts as well as the synthesis and secretion of collagen by these cells. The data demonstrate that angiotensin II, via AT1 receptors, can stimulate cardiac fibroblast growth and increase collagen synthesis in cardiac tissue. Thus, angiotensin II may contribute toward the development of cardiac hypertrophy in conditions of hypertension that are associated with elevated concentrations of angiotensin II.

Animals↗