Search PubMed⌕ Search

Biomedical subjects

M Acker

Publications and source records attributed to M Acker.

At least 19 recordsLinked to original sources
PubMed2004

An ultrafast time-resolved fluorescence spectroscopy system for metal ion complexation studies with organic ligands.

A dedicated spectrofluorimeter using ultrashort laser pulses as an excitation source was developed to measure the fluorescence properties of organic ligands for metal ion complexation with organic ligands. The laser system consists of an oscillator system for generation of femtosecond laser pulses, an amplifier system to increase the pulse energy of the generated pulses to about 2 mJ and an optical parametrical amplifier system to provide tunable laser pulses over a wide wavelength range (280 nm-10 microm). The laser pulses were applied to the sample and the emitted fluorescence was detected using a fast-gating intensified CCD camera-based spectrometer. To verify the performance of the laser, the well-known protonation constant [Pure Appl. Chem. 69 (1997) 329] of 2,3-dihydroxybenzoic acid was determined. The fluorescence lifetime of the excited species was determined as 375+/-32 ps in the pH range from 1.0 to 6.0, having a fluorescence emission maximum at 438 nm. The first protonation constant was determined from fluorescence data as log K(3)=3.17+/-0.05 at an ionic strength of 0.1 M and at 294 K exploiting the Stern-Volmer mechanism. The agreement of the protonation constant with literature data (log K(3)=3.10+/-0.20, I=0.1 M, T=298 K [Bull. Soc. Jpn. 44 (1971) 3459]) demonstrates the excellent performance of our system. Furthermore, we determined the complex formation constant log K(1)=-3.11+/-0.16 by measuring the fluorescence properties of the ligand for the 1:1 uranyldihydroxobenzoate complex in the pH range from 3.0 to 4.5 at ionic strength of 0.1 M and at 294 K. We also determined the complex formation constant via the fluorescence emission of the metal ion uranium(VI). The fluorescence of the uranyl ion is influenced by dynamic quenching of the non-dissociated ligand and by static quenching due to the complex formation. After correction of these effects using the determined fluorescence lifetime, the complex formation constant was calculated to be log K(1)=-3.99+/-0.44. A 1:1 metal:ligand stoichiometry was determined with both measurement methods. However, the difference of the obtained formation constants and the derived standard deviations indicate a superimposition of effects with the excited-state reactions of the ligand.

Carboxylic Acids↗
PubMed1999

Cytokines in Gaucher's disease.

Gaucher's disease (GD) is characterized by hepatosplenomegaly, bone marrow infiltration, osteonecrosis, which may all be associated with the presence of pathological macrophages that contain undegraded glycosphingolipids. Levels of serum cytokines, which are soluble products of mononuclear phagocytes (MNP), were evaluated in 24 GD patients. Levels of interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and soluble interleukin-2 receptor (sIL-2R) in GD patients were significantly higher than in normal controls. We attempted to correlate cytokine levels with disease severity. Type I GD patients with more severe clinical manifestations had significantly higher levels of IL-1beta, IL-1Ra and IL-6, relative to type I patients with milder disease. Three patients homozygous for the 1448C mutation with neuropathic type III disease, had significantly higher levels of sIL-2R than type I patients or controls. We speculate that cytokine over-expression may relate to the pathophysiology of some of the clinical manifestations of GD. Thus, the elevated IL-1beta, TNF-alpha and IL-6 levels may induce the bone manifestations, the neutrophil chemotaxis and the increased incidence of hyper-gammaglobulinemia present in GD patients.

Chemotaxis, Leukocyte↗
PubMed1997

Progressive angiomyolipoma with inferior vena cava tumor thrombus.

A 45-year-old man presented with an incidentally discovered benign renal angiomyolipoma. This lesion initially demonstrated renal vein involvement. On referral to our institution 3 years later, there was interval progression of tumor thrombus to the intrahepatic inferior vena cava. Intravascular extension of benign angiomyolipoma, though rare, has been reported. We present a new example and review the literature concerning this unusual complication of a common renal neoplasm.

Angiomyolipoma↗
PubMed1996

Effects of low-molecular-weight dermatan sulfate on coagulation, fibrinolysis and tissue factor pathway inhibitor in healthy volunteers.

Low-molecular-weight (LMW)-dermatan sulfate (Desmin) with the mean molecular weight of 5600 Da has been obtained by limited depolymerization of natural dermatan sulfate. The pharmacokinetic and pharmacodynamic data of 100 and 200 mg were analyzed after intravenous injection and of 50, 100 and 200 mg after subcutaneous injection on tissue factor pathway inhibitor (TFPI) antigen and activity, heparin cofactor (HC) II activity, HeptestTM coagulation value, chromogenic S-2222 anti-factor Xa (aXa) assay, activated partial thromboplastin time (APTT), thrombin clotting time (TCT), plasminogen, tissue plasminogen activator activity (t-PA) and plasminogen activator inhibitor (PAI). After i.v.injection of 100 mg and 200 mg Desmin TFPI antigen and activity increased 2.2- and 2.7-fold, and returned to normal values within 60 and 90 min, respectively. Using the HC II assay the elimination half-lives (T1/2 el) increased from 1.9 h to 3.3 h with increasing doses of LMW-dermatan sulfate. T1/2 el were 4.3 and 6.9 h with the Heptest assay and 3.3 and 5.1 with the aXa method, respectively. APTT, TCT and the fibrinolytic parameters were not modified by either dose of i.v. LMW-dermatan sulfate. After s.c. administration of 100 mg or 200 mg LMW-dermatan sulfate no increase of TFPI antigen or activity was detected. T1/2 el was 5.6 h using HC II method, 11.1 h using Heptest and 7.8 h with the aXa activity. The total clearance was about ten-fold higher when determined by the HC II method compared with Heptest and aXa method. The volume of distribution (VD) increased with increasing doses of s.c. LMW-dermatan sulfate and was highest with the HC II method. Intravenous administration of 100 mg protamine chloride 15 min after i.v. dosing of 100 mg LMW-dermatan sulfate did not modify TFPI, coagulation or fibrinolytic parameters. Further analysis of the complex mechanism of action has to include studies which should explain the low release of TFPI in relation to the antithrombotic effects of LMW-dermatan sulfate.

Anticoagulants↗
PubMed1996

Dynamic myoplasty: surgical transfer and stimulation of skeletal muscle for functional substitution or enhancement.

Dynamic myoplasty combines muscle transfer with electrical stimulation to provide contractile function that augments or replaces impaired organ function. Dynamic cardiomyoplasty was the first clinical application in which a skeletal muscle, latissimus dorsi, was transferred and stimulated to provide cardiac assistance, a function different from its original one. The problem of early muscle fatigue that was encountered in the initial implementation of the method was solved by training the muscle with electrical stimulation and thus changing its fiber composition. With intramuscular electrodes, the conditioned latissimus dorsi is stimulated in synchrony with the heart muscle. Safeguards are built into the two-channel implanted stimulator to avoid excessively high pulse rates. Clinicians report that 80% of patients with moderate to severe heart failure prior to operation showed a clinical improvement of 1.6 New York Heart Association classes. Alternative methods of providing cardiac assistance that are also being investigated include wrapping the muscle around the aorta, creating a skeletal muscle ventricle, and using the muscle to power an implantable pump. These latter techniques are still under preclinical investigation. Compared with heart transplant, cardiomyoplasty has the great advantage of not being subject to tissue rejection. The second principal application of dynamic myoplasty is treatment of fecal incontinence through creation of an electrically stimulated skeletal muscle neosphincter (ESMNS). The gracilis muscle of the leg is mobilized, wrapped around the anal canal, and conditioned with electrical stimulation to become more fatigue resistant. To achieve continence, the muscle is continuously stimulated except when the patient wishes to defecate. Overall success rates in achieving continence are 60-65%. Both cardiomyoplasty and the ESMNS technique, and their associated devices, are being refined through ongoing clinical trials.

Cardiomyoplasty↗
PubMed1995

Using the confluence model of sexual aggression to predict men's conflict with women: a 10-year follow-up study.

We tested a model describing the characteristics of sexually aggressive men that may also be useful for understanding the causes of other antisocial acts against women. This model hypothesizes that sexual aggressors can be identified by two sets of characteristics, labeled hostile masculinity and impersonal sex. To test this model, we followed up a sample of men 10 years after first studying them when they were young adults. We sought to predict which men would be in distressed relationships with women, be aggressive sexually, be nonsexually aggressive, or some combination of these. These behaviors were measured not only by questioning the men themselves but also by questioning many of the men's female partners. Some couples' videotaped conversations were also analyzed. The data supported the ability of the model to predict behavior 10 years later. We also developed the model further and identified the common and unique characteristics contributing to sexual aggression as compared with the other conflictual behaviors studied. The data supported the usefulness of hierarchical modeling incorporating both general factors that contribute to various interpersonal conflicts as well as specific factors uniquely pertaining to dominance of women.

Aggression↗
PubMed1991

Tricuspid valve myxoma: a rare indication for tricuspid valve repair.

Excision of a myxoma involving the tricuspid valve often necessitates tricuspid valve replacement or a less than optimal margin of resection. We report a successful tricuspid valve repair after en bloc resection of a myxoma involving the septal leaflet of the tricuspid valve.

Female↗
PubMed1991

Mitral valve repair in the extensively calcified mitral valve annulus.

Mitral valve replacement in patients with an extensively calcified mitral annulus is associated with an increased risk of ventricular rupture. Until now techniques of mitral valve repair have not been applied to patients with a heavily calcified mitral valve annulus. We present 12 patients who underwent extensive decalcification of the annulus with subsequent mitral valve repair between 1987 and 1990. Ages ranged from 11 to 78 years; 6 patients were in New York Heart Association functional class II, 4 were in class III, and 2 were in class IV. All patients had varying degrees of mitral insufficiency. There were no deaths, reoperations, or thromboembolic events. Postoperative echocardiography revealed minimal residual mitral insufficiency in only 2 of 12 patients. All patients are currently in New York Heart Association class I or II. We believe mitral valve repair can be done safely on patients with an extensively calcified mitral annulus, thus avoiding the risks of left ventricular rupture, thromboembolic events, and hemorrhagic complications associated with mitral valve replacement.

Adolescent↗
PubMed1991

Transabdominal esophagomyotomy and partial fundoplication for treatment of achalasia.

The most common surgical treatment for achalasia is a modified anterior extramucosal esophagomyotomy. Unfortunately, a poor outcome may result secondary to recurrent dysphagia or gastroesophageal reflux. The reported incidence of reflux is 4 to 50 per cent. Our treatment for achalasia is an esophagomyotomy carried onto the cardia combined with a partial gastric fundoplication. Of 22 patients who presented with achalasia and moderate to severe symptoms of dysphagia and odynophagia, 19 had this procedure performed. Of these 19 patients, only two required a second procedure (postoperative dilatation) for recurrent symptoms. All three patients who had a full fundoplication required further surgical correction. Although fundoplication has been condemned in the past as treatment of achalasia to avoid the postoperative outcome of reflux, we have been successful with a partial fundoplication added to the standard esophagomyotomy. Given the fine line that needs to be tread to prevent recurrent signs and symptoms of achalasia or reflux when performing esophagomyotomy, our procedure offers a viable alternative to transthoracic esophagomyotomy alone.

Adult↗
PubMed1989

Purification and biochemical characterization of recombinant hirudin produced by Saccharomyces cerevisiae.

Recombinant hirudin was produced by the yeast Saccharomyces cerevisiae using the alpha-pheromone prepro sequence to direct its secretion into the culture medium. The secreted hirudin was isolated to greater than or equal to 95% purity as measured by 205-nm absorbance integration from a reverse-phase chromatogram. One major activity peak corresponding to the complete, correctly processed molecule and two minor activity peaks corresponding to C-terminally truncated forms were identified. The primary structure of the major peak, determined by N-terminal sequencing of tryptic peptides, was that predicted from the cDNA sequence, and the molecular mass analyzed by fast atom bombardment mass spectrometry (FAB-MS) was 6892.6 (calculated 6892.5). UV spectral analysis suggested that, in contrast to the natural molecule, recombinant hirudin produced by S. cerevisiae is not sulfated.

Amino Acid Sequence↗
PubMed1989

Point mutations modifying the thrombin inhibition kinetics and antithrombotic activity in vivo of recombinant hirudin.

The hirudin variant HV2 was modified by in vitro site-specific mutagenesis of HV2 cDNA to generate HV2(Asn-47----Lys), HV2(Asn-47----Arg) and HV2(Lys-35----Thr, Asn-47----Lys). Residues 35 and 47 are positioned respectively within the finger and prothrombin-like domains of hirudin, both of which have been suggested as thrombin binding sites. The modified polypeptides were synthesized in Saccharomyces cerevisiae using a secretion vector and purified from culture supernatants. By analysis of the human alpha-thrombin:hirudin inhibition reaction in steady-state conditions it was shown that the dissociation constants for HV2(Lys-47) and HV2(Arg-47) were 5- to 14-fold lower than for unmodified HV2, whereas mutation of Lys-35 did not significantly alter the inhibition kinetics. Furthermore, HV2(Lys-47), whose sequence is identical to a natural hirudin variant, displayed enhanced anti-thrombotic activity in vivo, having a 100-fold lower ED50 compared to HV2 in the rabbit Wessler venous thrombosis model. These results support a role for the prothrombin-like domain in thrombin binding and, moreover, demonstrate that in vivo antithrombotic efficiency correlates with the dissociation constant of the inhibition reaction.

Amino Acid Sequence↗
PubMed1987

Oxygen consumption of chronically stimulated skeletal muscle.

The latissimus dorsi muscles of six dogs were made fatigue resistant by chronic electrical conditioning. Once the muscles were conditioned, oxygen consumption was measured during periods of exercise. The ratio of the tension developed to oxygen consumed during moderate stimulation (300 msec on) for the control and the electrically conditioned muscles was 16.3 +/- 3.5 and 36.5 +/- 6.7 kg-sec/ml oxygen, respectively. During intense stimulation (800 msec on) the ratio was 12.6 +/- 2.1 and 54.2 +/- 8.9 kg-sec/ml oxygen, respectively. Thus the conditioned muscle was able to develop and maintain tension with a considerably reduced oxygen expenditure. The increased efficiency of the conditioned muscle helps to explain its increased resistance to fatigue and the ability of pumping chambers constructed from electrically preconditioned skeletal muscle to perform sustained cardiac type work.

Animals↗
PubMed1985

Occult head injury: its incidence in spinal cord injury.

This study investigated the suspicion that a significant proportion of individuals having spinal cord injury (SCI) also sustain a concomitant undiagnosed occult head injury during the trauma accident. The criteria for high risk of head injury included the following: (1) quadriplegia with high energy deceleration accident, (2) loss of consciousness at time of injury, (3) brainstem or cortical neurologic indicators, or (4) respiratory support required at time of injury. In this study, 67 patients admitted to the rehabilitation unit were given a neuropsychologic evaluation a median of 48 days after injury. Motor free scales used were the Galveston Orientation and Amnesia Test (GOAT), Quick Test, Raven Progressive matrices, serial 7s, Shipley Hartford, Stroop Color/Word Interference, and the Wechsler Memory Scale Associate Learning Tests. Forty-three of the 67 patients (64%) scored mildly to profoundly impaired on the test battery. Evidence of poor premorbid academic history was present in 19 (44%) of those with impaired performance on the neurologic evaluation and in only three (13%) of those scoring unimpaired. Consequently, 56% (24/43) of the impaired had no previous record of scholastic difficulties, presumably acquiring cognitive impairment at the time of injury. The implications of this high incidence of impaired cognitive functioning for treatment of individuals with SCI are significant.

Adolescent↗