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Biomedical subjects

J Winkler

Publications and source records attributed to J Winkler.

At least 19 recordsLinked to original sources
PubMed1995

Essential role of neocortical acetylcholine in spatial memory.

The cholinergic system plays a crucial role in learning and memory. Lesions of cholinergic nuclei, pharmacological manipulations of cholinergic systems, intracerebral transplantation of fetal tissue and anatomical changes in cholinergic pathways during ageing have all been correlated with altered cognitive behaviour. However, it has not been proved that regional acetylcholine is causally required for learning and memory. Here we describe how we achieved a permanent and selective impairment of learning and memory by damaging the nucleus basalis magnocellularis, a nucleus that provides the major cholinergic innervation of the neocortex, in adult rats. To test the hypothesis that acetylcholine is essential for restoration of cognitive function, we implanted genetically modified cells that produce acetylcholine into denervated neocortical target regions. After grafting, rats with increased neocortical acetylcholine levels showed a significant improvement in a spatial navigation task. Acetylcholine is thus not only necessary for learning and memory, as previously argued, but its presence within the neocortex is also sufficient to ameliorate learning deficits and restore memory following damage to the nucleus basalis.

Acetylcholine↗
PubMed1995

Effects of nerve growth factor treatment on rats with lesions of the nucleus basalis magnocellularis produced by ibotenic acid, quisqualic acid, and AMPA.

Rats with bilateral lesions of the nucleus basalis magnocellularis (NBM) produced by ibotenic acid (IBO), quisqualic acid (QUIS), and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) received either human recombinant nerve growth factor (NGF) (5.0 micrograms/day) or cytochrome c (cc) (0.3 microgram/day) treatment. Spatial memory impairments in the Morris water maze differed for the three toxins in the following order: IBO-cc > AMPA-cc > QUIS-cc. Treatment with NGF resulted in behavioral improvement for only the IBO-lesioned rats. Body weight was not affected by the different lesions before treatment; however, administration of NGF resulted in a decreased rate of body weight gain independent of the excitotoxin used. Reduction in choline acetyltransferase (ChAT) activity differed in the neocortex for the three toxins, whereas the hippocampus was unaffected. The cortical ChAT depletion was greatest for AMPA, intermediate for QUIS, and least for IBO. Restoration of ChAT activity by NGF differed for the three toxins (QUIS-NGF > IBO-NGF > AMPA-NGF), whereas ChAT activity in the hippocampus was increased equally. The loss of low-affinity NGF-receptor (p75NGFr)-immunoreactive neurons differed for the toxins (AMPA-cc > QUIS-cc > IBO-cc), whereas treatment with NGF increased the size of the remaining neurons independently of the used toxin. NGF induced a p75NGFr-immunoreactive thickening around intracerebral arteries for all three toxins. Lesions of the NBM produced by IBO, QUIS, and AMPA resulted in a quantitatively different pattern of behavioral, biochemical, and histological deficits. The quantitatively different pattern of recovery after administration of NGF may be determined by the responsivity of the remaining neurons. Intracerebroventricular administration of NGF affected noncholinergic systems as well, resulting in decreased food intake and cerebrovascular hyperinnervation.

Animals↗
PubMed1995

Tetrameric structure and cellular location of catechol 2,3-dioxygenase.

Catechol 2,3-dioxygenase from the meta-cleavage pathway encoded on the TOL plasmid of Pseudomonas putida (pWWO) was investigated by electron microscopy. Negatively stained samples of the purified catechol 2,3-dioxygenase revealed that the enzyme consists of four subunits arranged in a tetrahedral conformation. Monoclonal antibodies raised against catechol 2,3-dioxygenase showed highly specific reactions and were used to localize the enzyme in Escherichia coli (pAW31) and P. putida (pWWO), using the protein A-gold technique carried out as a post-embedding immunoelectron microscopy procedure. Our in situ labeling studies revealed a cytoplasmic location of the catechol 2,3-dioxygenase in both cell types.

Antibodies, Monoclonal↗
PubMed1992

CAPD versus haemodialysis: a comparison in the same patients.

Most studies comparing CAPD and haemodialysis (HD) were done in different populations, matched for sex and age. The present report compared 13 non-diabetic end-stage renal failure patients who were treated for at least six months with each type of therapy. Analysis of the data revealed a higher haemoglobin during CAPD but no differences in the blood transfusion requirements. Serum creatinine, BUN and potassium were lower during CAPD and serum calcium was higher during HD. Serum cholesterol levels were higher during CAPD and returned to pre-CAPD levels during the fourth month after being transferred to HD. Hospitalization rates were similar with the two treatments. Our study confirmed previous sex- and age-matched studies comparing CAPD and HD therapy.

Blood Transfusion↗
PubMed1992

Acute decline in renal function as a consequence of ovarian hyperstimulation syndrome.

Two cases of severe ovarian hyperstimulation syndrome following ovulation induction are described, one of them following in vitro fertilization and embryo transfer, and the other after conventional ovarian stimulation. This condition was associated with an acute reversible decline in renal function. The treatment and the possible pathophysiological mechanisms are discussed.

Adult↗
PubMed1992

Transcranial color-coded real-time sonography in the evaluation of intracranial neoplasms and arteriovenous malformations.

Transcranial color-coded real-time sonography (TCCS) was performed in 57 patients with primary intracranial brain tumors (n = 49) or arteriovenous malformations (n = 8) to evaluate its diagnostic potential. In 46 patients (81%), lesions could be identified employing this technique. In 7 patients, transcranial ultrasound examination was not feasible because of bone thickness; in the remaining 4 patients, the tumor was indistinguishable from adjacent brain tissue despite sufficient insonation, suggesting that these neoplasms are isoechogenic. The sonographic features of brain tumors were very similar: a hyperechogenic matrix of the lesion was interspersed by hypoechogenic pixels. Larger hypoechogenic areas (0.5-1 cm) gave evidence of tumor necrosis. Differences between the findings of TCCS and computed tomography concerning tumor size were found in 7 patients, in whom TCCS revealed an area of smaller extension within the corresponding hypodense area on the computed tomographic scan. Perifocal brain edema could not be detected by ultrasound examination. In 13 patients, a thin, hypoechogenic peritumoral halo was disclosed that did not correlate with perifocal brain edema identified by computed tomography and that may have been due to compression of adjacent parenchyma. In patients with arteriovenous malformations, TCCS permitted the identification of the main feeders, the nidus, and the draining venous system by color-coded depiction of intravascular blood flow. In conclusion, TCCS is an additional method for initial diagnosis and highly suitable for follow-up in tumor patients and provides valuable information about tissue characteristics and blood flow.

Adult↗
PubMed1992

Causes of death in patients with end-stage renal disease treated by dialysis in a center in Israel.

The causes of death in 84 end-stage renal failure patients, treated with dialysis, who died during a 66-month period were reviewed retrospectively. Cardiac and infectious diseases were the main cause of death (27% each). These two constituted 44% of causes of death in hemodialysis and 75% in continuous ambulatory peritoneal dialysis patients. Malignant disease (7%) and hyperkalemia (5%) were responsible for death only in hemodialysis patients. Patients who died following hyperkalemia were younger than 50 years old. Patients who died from malignant disease were dialyzed for more than 3 years. In summary, the mode of dialysis therapy, age at start of therapy, time on dialysis, and previous cardiac disease may play a role in determining the causes of death in dialysis patients.

Adolescent↗
PubMed1992

[The effect of arteriosclerosis on the wall elasticity of the human common carotid artery].

The arterial distensibility and the modulus of volume elasticity of more than 100 isolated human carotid arteries was measured and correlated with arteriosclerosis and aging. The loss of arterial distensibility progresses steadily with aging. Arteries with severe arteriosclerosis and arteries with minimal arteriosclerosis show almost similar distensibility. On the other side the differences between distensibility of arteries with moderate arteriosclerosis and arteries with minimal as well as severe arteriosclerosis, especially in the younger and middle ages, are significant.

Aging↗
PubMed1991

A successful treatment of an intrarenal arteriovenous fistula by percutaneous embolization.

A 37-year-old woman patient, known to have poorly controlled arterial hypertension that was diagnosed following a cerebrovascular accident at the age of 15 years, was referred to our outpatient clinic for investigation in 1987. An intrarenal arteriovenous fistula was diagnosed by selective renal angiography. Embolization of the fistula was performed using four 15-mm/5-cm coils, which induced thrombosis and obstructed the fistula. The vascularization of the affected kidney improved immediately. During the following 4 months, the antihypertensive treatment was stopped gradually, and the patient remained normotensive. This is an unusual case of a large intrarenal arteriovenous fistula, whose etiology was not clear, that was successfully treated by percutaneous embolization.

Adult↗
PubMed1991

[Transcranial color-coded real-time sonography in the adult. 1: Normal findings and cerebrovascular ischemia].

Transcranial colour-coded real time sonography (TCCS) is a new, non-invasive diagnostic bedside procedure allowing two-dimensional imaging of cerebral parenchymatous structures and large intracranial arteries through the intact skull. So far we examined a population of 183 patients und 53 normal subjects, all above 18 years of age. 24 (10%) subjects were not suitable for examination. Two-dimensional imaging of telencephalic, diencephalic, mesencephalic and pontine structures is feasible. Intravascular blood flow phenomena may be analysed quantitatively by an integrated pulsed wave Doppler system. The diagnosis of arterial stenosis and occlusion could be established in 14 patients each by analysing the colour-coded B-mode image and Doppler frequency spectrum. TCCS may complement diagnostic tools in neurology and may improve standardisation of transcranial Doppler measurements.

Adult↗
PubMed1991

[Transcranial color-coded real time sonography in adults. Part 2: Cerebral hemorrhage and tumors].

We examined three groups of adult patients to evaluate the clinical application of transcranial colour-coded real-time sonography (TCCS): 28 patients suffering from intracerebral haemorrhage, 36 patients with subarachnoid haemorrhage and 38 patients with primary brain tumours. All sonographic examinations were performed through the intact skull. Cerebral haemorrhages were visualised via TCCS as hyperechogenic areas, which were closely correlated in size and location to CT findings. Apart from the imaging of subarachnoid haemorrhages and cerebral vasospasms, TCCS permitted the identification of the angiographically confirmed aneurysms in 76%. Brain tumours were delineated in the vast majority of the patients examined. In this type of pathology TCCS provided additional information on tumour extension and macroscopic appearance.

Adult↗
PubMed1991

Inhibition of angiotensin converting enzyme by ramipril in serum and tissue of man.

Studies in animal models have indicated that ramipril is a potent inhibitor of angiotensin converting enzyme (ACE) in serum and tissue. In our study, the normal range of ACE activity and the inhibitory effect of short-term oral administration of ramipril on ACE activity in human serum and tissue samples of renal cortex, heart and blood vessels were determined. ACE activity in the renal cortex (125.2 +/- 11.5 nmol/mg per min) was greater than 600 times that of the heart (0.20 +/- 0.01 nmol/mg per min), greater than 500 times that of the veins (0.23 +/- 0.09 nmol/mg per min) and greater than 150 times that of the arteries (0.80 +/- 0.23 nmol/mg per min). ACE activity in the renal cortex and arteries 2 h after last dosing was almost completely inhibited by ramipril whereas ACE activity in the veins and heart was inhibited to a lesser extent. Our results demonstrate in man, for the first time, an inhibition of tissue ACE following short-term oral treatment with an ACE inhibitor.

Administration, Oral↗
PubMed1991

Diagnosis and monitoring of subarachnoid hemorrhage by transcranial color-coded real-time sonography.

Thirty-six patients with acute spontaneous subarachnoid hemorrhage (26 caused by rupture of an aneurysm) were examined by transcranial color-coded real-time sonography by using a 2.25-MHz ultrasound transducer. In 20 of these 26 patients (76%), the aneurysm could be identified by a characteristic abnormal blood flow pattern within the aneurysm in coronal and axial scanning planes by transcranial color-coded real-time sonography. Blood within the basal cisterns, on top of the tentorium, and within the ventricles and parenchyma was sonographically detected by increased echodensity in 75%. In addition, cerebrospinal fluid circulation disturbances and cerebral vasospasm were detected in two-dimensional B-mode images in 85% and 100%, respectively. In Doppler mode, intravascular blood flow velocity could be quantified. We conclude that transcranial color-coded real-time sonography, a new, noninvasive method for diagnosis and follow-up of patients with subarachnoid hemorrhage, allows detection of the primary vascular lesion and monitoring of complications.

Blood Flow Velocity↗
PubMed1991

Defective polymorphonuclear leukocyte formyl peptide receptor(s) in juvenile periodontitis.

Juvenile periodontitis (JP) is a disease characterized by severe gingival infections. PMN from some JP patients exhibit abnormal chemotactic responsiveness when challenged with the synthetic formyl peptide, FMLP. While investigating PMN function in JP, we found a patient in whom abnormal PMN chemotactic responses to FMLP were associated with a defective population of PMN formyl peptide receptor(s) (FPR). JP PMN failed to respond chemotactically when challenged with FMLP, but exhibited normal chemotactic responses upon exposure to purified human C5a. Furthermore, JP PMN were capable of degranulating and generating superoxide anion radicals as well as normal PMN upon exposure to FMLP. Binding studies demonstrated that JP PMN had a diminution in the number of high-affinity FPR. Studies in which FPR was radiolabeled by chemical cross-linking demonstrated that JP PMN FPR exhibited the same molecular weight and N-linked glycosylation as normal PMN FPR. JP PMN FPR, however, was more resistant to papain cleavage than normal PMN FPR. Autoradiograms obtained from 2D-PAGE of normal and JP PMN FPR demonstrated decreased amounts of FPR isoforms in JP PMN.

Adult↗
PubMed1991

[Modification of pulmonary hypertension in patients with chronic obstructive lung diseases by trapidil (Rocornal) in an acute trial].

Acute effects of Trapidil (Rocornal, Deutsches Hydrierwerk Rodleben) on pulmonary hemodynamics were studied in 47 patients. A marked decrease of pulmonary artery pressure, pulmonary vascular resistance and of right ventricular stroke work at rest and during exercise in different degrees of severity of pulmonary hypertension was shown. Especially the influence on stable pulmonary hypertension is of interest, but there was no statistical significance during exercise because of the small number of patients. Considerable objective or/and subjective side effects were not noticed. Possible multifactorial mechanisms of these effects including the left ventricular function and the role of prostaglandins are discussed. The effect of trapidil is compared with other investigated pulmonary vasodilators, such as nitrates and nifedipine. Because of hitherto there are no other studies with Rocornal in patients with COPD, further acute studies and placebo controlled long term studies with monitoring of pulmonary hemodynamic are necessary. Than it will be possible to clarify the role of trapidil in therapeutical concepts of pulmonary hypertension.

Adult↗
PubMed1990

[Lactic acidosis].

The rare congenital lactic acidosis is a consequence of enzyme defects. The acquired form is relatively common in critically ill patients. The altered metabolism of pyruvate and the imbalance between lactate production and utilization have a central role in the pathogenesis of this disease. The physiologic compensating mechanisms are generally not sufficient for complete correction of acidosis. In most of the cases the basic disease is the one that should be treated. The correction of the acidosis must be careful, because overtreatment may worsen acidosis, or may cause severe post-treatment alkalosis.

Acidosis, Lactic↗