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Biomedical subjects

H J Berger

Publications and source records attributed to H J Berger.

At least 19 recordsLinked to original sources
PubMed1992

Transcriptional regulation in cardiac muscle. Coordinate expression of Id with a neonatal phenotype during development and following a hypertrophic stimulus in adult rat ventricular myocytes in vitro.

The transcriptional regulatory mechanisms in heart muscle that direct cardiac development and allow for a flexible, adaptive response to physiologic stress are not well understood. We demonstrate that a negative regulator of gene transcription termed Id that has been described predominantly in proliferating cell lines and in undifferentiated tissue during growth, is expressed in freshly isolated terminally differentiated adult rat ventricular myocytes, in contrast to most other tissues in the adult rat. Id mRNA expression is regulated in ventricular myocytes during post-natal development, peaking at the transition from hyperplastic to hypertrophic growth at day 17 in the rat, declining subsequently to lower, stable levels in adult myocytes. Although Id mRNA becomes undetectable in adult ventricular myocytes 48 h following isolation in the absence of serum, it can be rapidly reinduced by an alpha-adrenergic agonist, accompanied by increased protein synthesis and the reexpression, in defined media, of the neonatal genes prepro-ANP and skeletal muscle alpha-actin. Thus, the differential regulation of Id during cardiac development, the presence of Id mRNA in normal cardiac myocytes, and its increased expression following a hypertrophic stimulus all suggest a role for this transcriptional regulator in the control of cardiac muscle cell phenotype.

Aging↗
PubMed1992

Imaging of vascular injury with 99mTc-labeled monoclonal antiplatelet antibody S12. Preliminary experience in human percutaneous transluminal angioplasty.

BACKGROUND: To evaluate the in vivo safety, biodistribution, and diagnostic accuracy of a monoclonal Fab' antibody (S12) that is specific for the platelet membrane glycoprotein (GMP-140) expressed during platelet activation at vascular injury sites, 11 peripheral percutaneous transluminal angioplasty (PTA) patients (age, 61 +/- 8 years) with severe vascular disease had serial 99mTcS12 radionuclide imaging at 5 and 90 minutes, 4-6 hours, and 20-24 hours after a total of 23 angiographically successful PTA procedures. No acute allergic reactions or hematologic toxicity occurred. METHODS AND RESULTS: The average PTA percent angiographic diameter stenosis (DS) at all 23 sites decreased from 85 +/- 12% to 12 +/- 11%, with a mean before-to-after-PTA change of 73 +/- 14% (p less than 0.01). The mean radionuclide image-derived ratio of 99mTc S12 activity in PTA versus contralateral non-PTA arterial segments for all angioplasty sites was 1.6 +/- 0.5. Vascular 99mTc S12 antibody activity was qualitatively evident in the majority (78%) of PTA sites at 4-6 hours after injection. 99mTc S12 target-to-background (muscle) ratio equaled 2.3 +/- 0.6 at PTA sites. Nine PTA sites (39%) had residual 99mTc S12 activity at 24 hours after injection (mean PTA site-to-contralateral artery ratio, 1.5 +/- 0.4). The mean vascular 99mTc S12 activity ratios in 10 procedurally complicated (defined as extensive dilation [greater than 2 cm] or grade I or greater arterial dissection) and 13 uncomplicated PTA segments were 1.9 +/- 0.5 versus 1.2 +/- 0.1, respectively (p less than 0.01). The associated before-to-after-PTA angiographic improvement was significantly less in procedurally complicated PTA sites (66 +/- 12% versus 80 +/- 12% DS; p less than 0.01). CONCLUSIONS: 99mTc S12 activity is significantly increased at angiographically patent PTA sites that are procedurally complicated and are associated with less significant before-to-after-PTA angiographic improvement. 99mTc S12 monoclonal Fab' antibody imaging permits noninvasive identification of local vascular platelet activation resulting from angioplasty balloon injury in humans.

Angioplasty, Balloon↗
PubMed1992

An instant kit method for labeling antimyosin Fab' with technetium-99m: evaluation in an experimental myocardial infarct model.

An instant kit method for labeling antibody Fab' fragments was developed. The method utilizes a ligand exchange reaction between the intermediate complex 99mTc-D-glucarate and the free sulfhydryl groups on the antibody Fab' fragment. Radiolabeling of the Fab' using generator eluate achieves quantitative 99mTc incorporation in less than 30 min at room temperature. The radiolabel is stable in human plasma for at least 24 hr and stable to incubation with 10 mM diethylene-triaminepentaacetic acid (24 hr) and 1 mM diaminodithiol agent (up to 3 hr). Mouse biodistribution of 99mTc-antimyosin shows faster blood clearance and lower uptake in the lungs, liver, and spleen in comparison to 111In-antimyosin. Technetium-99m-antimyosin and 111In-antimyosin showed equivalent ability to detect myocardial infarct in a canine model.

Animals↗
PubMed1991

The oxime HGG-12 as a muscarinic acetylcholine receptor antagonist without intrinsic activity in cardiac membranes.

Direct interactions of the bispyridinium oxime HGG-12 with muscarinic acetylcholine receptors were investigated in porcine cardiac atrial membranes. Competition binding experiments using the radiolabeled muscarinic receptor antagonist (3H)QNB revealed specific binding of HGG-12 to muscarinic acetylcholine receptors of porcine atrial membranes with a dissociation constant of 3.8 x 10(-7) mol/l. Muscarinic acetylcholine receptor-stimulated binding of the radiolabeled GTP analog (35S)GTP[S] to guanine nucleotide binding proteins (G-proteins) was used to study antagonistic and possible agonistic effects of HGG-12 at muscarinic acetylcholine receptors. HGG-12 completely inhibited carbachol- and oxotremorine-stimulated (35S)GTP[S] binding to pertussis toxin sensitive and insensitive G-proteins in a competitive manner. Inhibition constants (K1) of HGG-12 for blockade of carbachol- and oxotremorine-stimulated GTP[S]-binding (9.7 x 10(-7) mol/l and 1.7 x 10(-6) mol/l, respectively) were higher by about a factor of 100 than those of the muscarinic acetylcholine receptor antagonist atropine. In the absence of muscarinic acetylcholine receptor agonists. HGG-12 by itself had no stimulatory effect on (35S)GTP[S] binding in porcine atrial membranes. The results of this study show that the oxime HGG-12 is a competitive antagonist without intrinsic activity at porcine atrial muscarinic acetylcholine receptors. The stimulatory action of HGG-12 on muscarinic acetylcholine receptors which has been described by several authors is, therefore, suggested to be due to partial inhibition of acetylcholinesterase by the oxime rather than to direct agonism at muscarinic acetylcholine receptors.

Animals↗
PubMed1991

In vivo technetium-99m S12 antibody imaging of platelet alpha-granules in rabbit endothelial neointimal proliferation after angioplasty.

To examine the specificity of technetium-99m monoclonal antibody (S12) imaging for identifying activated platelets at interventional injury sites in atherosclerotic rabbit arteries, subgroups of unheparinized rabbits (n = 39) underwent serial percutaneous transluminal aortic angioplasty (PTA) procedures (with or without intravascular stent placement) followed by in vivo and then ex vivo gamma camera imaging, scanning, and immunoelectron microscopy to determine the intravascular loci of S12 Fab' antibody binding. Despite angiographic vessel patency, image-derived ratios of in vivo S12 binding in injured versus uninjured vascular segments were significantly increased (p less than 0.05) after one PTA (1.3 +/- 0.17, n = 7), PTA twice at 6-week intervals (1.4 +/- 0.22, n = 7), and PTA plus stent placement (1.6 +/- 0.28, n = 7) compared with control experiments (1.1 +/- 0.13, n = 7). Ex vivo imaging of blood-free excised aortas confirmed S12 localization at PTA (2 +/- 0.4, n = 3) and PTA plus stent placement (5 +/- 3.8, n = 7) sites (both p less than 0.05 versus controls). S12 antibody uptake decreased significantly (p less than 0.05) at 1 week after PTA plus stent placement in vivo (1.1 +/- 0.10, n = 4) and ex vivo (1.6 +/- 0.7, n = 3). Electron microscopic studies confirmed dense platelet, fibrin, and red blood cell deposition in regions of acute injury, with endothelial neointimal proliferation at 1 week after PTA. Immunoelectron microscopic studies confirmed specific in vivo S12 binding (22:1 versus nonrelevant IgG) at sites of alpha-granule GMP-140 expression in activated platelets. Therefore, S12 studies may be useful to localize sites of platelet-derived mitogen release at arterial PTA injury sites.

Angioplasty, Balloon↗
PubMed1991

Effect of positive inotropic agents on myosin isozyme population and mechanical activity of cultured rat heart myocytes.

To examine whether catecholamines have a direct effect on myosin heavy chain expression of heart myocytes or whether they act via an altered work load, myocytes from neonatal rat hearts were cultured in thyroid hormone-free media containing various positive inotropic and chronotropic agents. The velocity and frequency of contraction of the myocytes were monitored using an optoelectronic system. After 3-5 days of culture, myosin isozyme populations, cellular cAMP content, and 2-deoxy-D-glucose uptake of the myocytes were determined. Compared with myocytes cultured in the absence of inotropic agents (32.6 +/- 3.5% V1), the proportion of myosin V1 was significantly (p less than 0.05) increased in the case of 1 microM isoproterenol (48.2 +/- 5.9% V1), 1 microM forskolin (57.1 +/- 11.7% V1), and 1 mM dibutyryl cAMP (79.1 +/- 2.0% V1). Dibutyryl cAMP increased V1 to a similar level as 30 nM triiodothyronine did (70.2 +/- 13.0% V1). Only a small increase was observed in myocytes cultured in the presence of 10 microM phenylephrine (40.4 +/- 8.4% V1), 10 microM ouabain (40.6 +/- 11.9% V1), or 10 microM Bay K 8644 (40.7 +/- 11.7% V1). The agents with a marked effect on myosin heavy chain expression resulted in a higher cAMP content; isoproterenol and forskolin also stimulated 2-deoxy-D-glucose uptake. All agents resulted in a higher velocity of contraction; with the exception of ouabain, frequency of contraction was also increased. A change in Ca2+ concentration in the medium from 1.3 to 2.4 mM resulted in a small increase in V1 (40.7 +/- 5.2% V1) but had the same effect on contraction velocity as dibutyryl cAMP did. Furthermore, 10 nM isoproterenol also increased V1 in myocytes that were arrested with 10 microM verapamil. The increase in V1 in the case of dibutyryl cAMP, isoproterenol, and forskolin is thus most probably not a correlate of the increased mechanical activity but of the high cellular cAMP content.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Evaluation of indium-111-labeled antifibrin monoclonal antibody for the diagnosis of venous thrombotic disease.

The potential advantage of using 111In-antifibrin (111In-AF) monoclonal antibody for the diagnosis of deep venous thrombosis (DVT) was studied in 44 patients with suspected DVT (27 underwent heparin therapy before 111In-AF injection). All patients had contrast venography (considered as the gold standard) and 111In-AF scintigraphy within 24 hr. Two to 3 mCi of 111In-AF were injected intravenously, and planar scintigraphy of the limbs was recorded within 10 min (17 times), 3 hr (44 times), and 18 hr (39 times). Indium-111-AF images were then interpreted without knowledge of the results of the other examinations. The DVT diagnostic accuracy of 111In-AF was greater when interpretation was based on images recorded at different time periods after injection. Indium-111-AF sensitivity for diagnosis of DVT was 85% (29/34) and was not apparently decreased by heparin therapy. None of the 10 patients with negative contrast venography had a positive 111In-AF scan. The results demonstrate the importance of recording serial images and the excellent accuracy of 111In-AF for diagnosing DVT.

Antibodies, Monoclonal↗
PubMed1990

Detection of thrombophlebitis with 111In-labeled anti-fibrin antibody: preliminary results.

Deep venous thrombosis remains a major medical problem, affecting a large segment of the population and resulting in significant mortality and morbidity. Current techniques available for detecting deep venous thrombosis present limitations that may mitigate their potential benefit to the patient. Invasive techniques, such as ascending contrast venography, carry risks to the patient with regard to complications such as an allergic reaction to an iodine dye, adverse effects to renal functions, and clot formation in a normal vein. Noninvasive techniques, such as Doppler ultrasound and impedance plethysmography, evaluate only a limited segment of the venous bed. The need remains for a diagnostic technique that is safe, accurate, and widely accessible. A readily available noninvasive scintigraphic technique utilizing radiolabeled monoclonal anti-fibrin antibody may overcome some of these shortcomings. This imaging examination is quite effective in detecting clots in the lower extremities. Compared to contrast venography, 111In-labeled anti-fibrin antibody imaging appears to be as sensitive in identifying acute venous thrombosis. In addition, the preliminary data indicate that anticoagulation with heparin may interfere with adequate visualization of the clots with this technique.

Adult↗
PubMed1990

Which risk factors predict the levodopa response in fluctuating Parkinson's disease?

Three putative risk factors to the pathogenesis of end-of-dose-related fluctuations--severity of Parkinson's disease (PD), duration of PD, and duration of levodopa therapy--were evaluated in 39 patients with PD by measuring response duration and response magnitude to a single levodopa dose. After discontinuing levodopa therapy for 12 hours, the motor status of each patient was assessed before a single dose of 100 mg of levodopa plus 25 mg of decarboxylase inhibitor was given and at five 45-minute intervals thereafter. Multiple regression analysis showed that the response duration was best predicted by the severity of PD. The response magnitude was significantly correlated both to the duration of PD and to the duration of levodopa therapy. It is argued, however, that the response magnitude was predicted by the duration of levodopa therapy. Our results are in accordance with those of other recent studies and indicate that variances in levodopa response duration and in levodopa response magnitude are caused by their own differential risk factor.

Adult↗
PubMed1990

Severity of Parkinson's disease is a risk factor for peak-dose dyskinesia.

Fifty four patients with idiopathic Parkinson's disease receiving levodopa therapy were studied. Thirty three of these patients displayed peak-dose dyskinesia. Neither the duration of Parkinson's disease nor the duration of levodopa therapy discriminated between patients with and patients without peak-dose dyskinesia. Consequently, these criteria could not determine whether the first appearance of peak-dose dyskinesia depends on the duration of Parkinson's disease--a factor that is related to the severity of the disease--or on the duration of levodopa therapy. A subgroup of nineteen patients with unilateral or unequivocally asymmetrical peak-dose dyskinesia was examined 12 hours after withdrawal of levodopa. A levodopa testdose provoked unilateral or unilateral preponderant peak-dose dyskinesia which always involved the most severely affected side and which also happened to be the side of onset of the disease. This demonstrates that the severity of Parkinson's disease is the main risk factor for peak-dose dyskinesia.

Aged↗
PubMed1990

Bimanual simultaneous motor performance and impaired ability to shift attention in Parkinson's disease.

The ability to share time and to shift attention between bimanual simultaneous motor tasks were studied in 18 patients with Parkinson's disease (PD) and 19 age- and intelligence-matched controls. The task consisted of drawing triangles with the dominant hand and squeezing a rubber bulb with the nondominant hand. Motor performance was measured using the variables: amplitude of squeezing, frequency of squeezing and velocity of drawing triangles. After eliminating variance due to baseline differences in single-handed performance, the bimanual simultaneous performance of PD and controls turned out to be similar to the frequency of squeezing and the velocity of drawing triangles. The amplitude of squeezing, however, differed between the two groups: it was significantly reduced in PD. Arguably the disturbance in the bimanual performance of PD patients was not due to a disorder of time sharing, but to a decreased ability to shift attention from the visually cued task to the non visually cued task. The results agree with current evidence that PD patients are more impaired when they have to rely upon internal control for the regulation of shifting attention than when external cues are available.

Aged↗
PubMed1990

Radiolabeled antifibrin antibody in the detection of venous thrombosis: preliminary results.

The recent development of monoclonal antibodies against components of coagulated blood may provide new approaches to the diagnosis of venous thrombosis. Scanning with an indium-111-labeled Fab fragment of a murine monoclonal antifibrin antibody (59D8) and ascending contrast venography were performed in 33 patients. Images of the calves, popliteal fossae, thighs, and pelvis were obtained immediately, 4-6 hours, and 24 hours after injection of 2 mCi (74 MBq) of the antibody. All images were read in a blinded manner. Findings in both studies were positive in 28 patients and negative in three. In 19 patients not undergoing heparin therapy, 19 specific anatomic sites were positive on venograms and 29 were positive on antibody images (19 sites matched). In 14 patients undergoing heparin therapy, 34 sites were positive on venograms and 27 were positive on antibody images (22 sites matched). In most patients, positive results were noted within 1 hour of antibody injection. No adverse effects were noted with the antibody preparation. Preliminary data suggest that antifibrin antibody imaging is sensitive in detecting clots, is safe to use, and may have a role in diagnosing and managing venous thrombosis.

Adult↗
PubMed1989

Evaluation of a serologic marker, CA19-9, in the diagnosis of pancreatic cancer.

STUDY OBJECTIVE: To determine the utility of the serologic marker CA19-9 in the diagnosis of pancreatic cancer in patients suspected of having a pancreatic disorder. DESIGN: Blinded study of frozen pedigreed serum samples collected at time of diagnostic evaluation with follow-up review at a mean of 8 years. SETTING: A general university teaching hospital serving both primary and referral patient populations. MEASUREMENTS AND MAIN RESULTS: Sera collected prospectively from 1978 to 1980 from 261 patients undergoing imaging studies of the pancreas (ultrasound, computed tomography, endoscopic retrograde cholangiopancreatography) for a variety of symptoms were assayed for CA19-9 levels, and the results were compared with earlier determinations of other potential markers for pancreatic cancer. In 54 patients ultimately shown to have pancreatic cancer, the CA19-9 assay showed a sensitivity of 70% with a median value of 349 u/mL (normal less than 70 u/mL) and range, 7.3 to 2,859,964 u/mL, whereas specificity of the marker in this population was 87%. The positive predictive value was 59%, and the negative predictive value was 92%. Results of CA19-9 testing in the small group of patients with definitive staging information showed no difference in sensitivity between patients with local/regional disease (n = 6) and those with distant metastases (n = 14), 50% compared with 71% (P = 0.613). CONCLUSION: CA19-9 was found to be a more sensitive and specific marker of pancreatic cancer than other serologic markers and should be a useful test in the patient with suspected pancreatic disease.

Adenocarcinoma↗
PubMed1989

Sequential multivessel coronary angioplasty assessed by thallium-201 tomography.

In 11 patients with multivessel coronary artery disease, SPECT thallium-201 imaging was performed prior to and within 3 days after each of two sequential percutaneous transluminal coronary angioplasties on separate days designed to achieve total revascularization. Thallium-201 SPECT was analyzed quantitatively, and an ischemic score for the vascular bed(s) supplied by the dilated vessel(s) was derived. For the vessels dilated during the first procedure the mean diameter stenosis was 80 +/- 8%, reduced to 27 +/- 9%. For the second procedure mean stenosis was reduced from 67 +/- 10% to 26 +/- 6%. For the two procedures, the mean thallium scores decreased from 298 +/- 225 to 115 +/- 130 (P less than .001) and from 135 +/- 129 to 46 +/- 60 (P less than .001), respectively. Of 10 patients with abnormal thallium-201 SPECT prior to angioplasty, nine improved after the first procedure, and seven improved further following the second procedure. Thus, utilizing staged angioplasty with a strategy of dilating the most severe lesion first, thallium-201 SPECT documented progressive improvement in myocardial perfusion.

Angioplasty, Balloon, Coronary↗
PubMed1989

Haloperidol and cognitive shifting.

In this study haloperidol appeared to affect the performance on a selected category of cognitive tasks considered to represent shifting aptitude. A pretest--post-test design was used with two groups of subjects: 17 patients suffering from idiopathic spasmodic torticollis, and 17 controls who were matched for age and intelligence. The results are discussed in relation to previous findings on haloperidol and cognition, shifting disorder in Parkinson's disease and changes in behavioural organization found in animals with an experimentally induced dopaminergic hypoactivity.

Attention↗