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Biomedical subjects

W Berger

Publications and source records attributed to W Berger.

At least 127 records · Page 7Linked to original sources
PubMed1993

Adenosine A1 receptors in human hippocampus: inhibition of [3H]8-cyclopentyl-1,3-dipropylxanthine binding by antagonist drugs.

Adenosine A1 receptors were visualized in human hippocampus using [3H]8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as a radioactive ligand probe. The receptor antagonists caffeine, the xanthine derivative KFM 19 and the carbamazepine analogue oxcarbazepine displaced [3H]DPCPX binding homogeneously without any marked difference between the individual layers in the investigated hippocampal subregions (n = 4). Ki's in the individual layers were in a range between 8.5 +/- 6.5 microM and 18.9 +/- 16.0 microM for caffeine and 11.5 +/- 2.8 nM and 18.1 +/- 14.1 nM for KFM 19. Ki's could not be calculated for oxcarbazepine as the IC50's were greater than 100 microM with estimated IC25's varying between 51.2 +/- 53.3 microM and 179.9 +/- 89.9 microM. Antagonism of endogenous adenosine at A1 receptors may thus explain part of the clinical effects of caffeine in humans and possibly exclusively the behavioral effects of KFM 19 in non-human primates.

Aged↗
PubMed1993

Identification of a yeast artificial chromosome (YAC) spanning the synovial sarcoma-specific t(X;18)(p11.2;q11.2) breakpoint.

A somatic cell hybrid containing the synovial sarcoma-associated t(X;18)(p11.2;q11.2) derivative (der(X)) chromosome was used to characterize the translocation breakpoint region on the X chromosome. By using Southern hybridization of DNA from this der(X) hybrid in conjunction with Xp-region specific radiation reduced cell hybrids and probes, it was found that this breakpoint maps within the ornithine aminotransferase (OAT) L1 cluster. A yeast artificial chromosome (YAC) clone (OAT YAC2) which hybridizes to a human OAT cDNA probe and is known to contain part of the OATL1 cluster was selected and used to confirm these results both by fluorescence in situ hybridization on synovial sarcoma patient material and by hybridization of its end-clones to the der(X) containing hybrid cells. It was found that indeed the human Xp sequences contained within this YAC are split as a consequence of the (X;18) translocation. Therefore, we conclude that OAT YAC2 spans the synovial sarcoma-specific translocation breakpoint and, as such, may serve as an ideal starting point from which the gene(s) involved in the development of this soft tissue tumor can be isolated.

Animals↗
PubMed1993

Human stance on a sinusoidally translating platform: balance control by feedforward and feedback mechanisms.

With subjects standing on a treadmill moving sinusoidally backward and forward, recordings of electromyographic (EMG) leg and trunk muscle activity, head and joint movements and platform torque were made with the subjects' eyes open or closed. The sinusoidal frequency was changed, stepwise and randomly, between 0.5, 0.3 and 0.25 Hz. The amplitude of the deflection was constant at +/- 12 cm. During an adapted sinus cycle, the maximum leg muscle EMG activity was recorded in the tibialis anterior around the posterior turning point and in the gastrocnemius around the anterior turning point in the treadmill cycle. This activity was associated with a forward inclination of the body around the posterior point and a straightening of the body at the anterior point. Both the degree of body inclination and the corresponding EMG activity were dependent upon the sinusoidal frequency. The programmed adjustment of the body inclination was such that the result of inertial and gravitational forces acting on the body coincided with the axis of the body at the posterior turning point. At the anterior point, the adjustment was achieved mainly by strong activation of the leg extensors. The latencies of the compensatory muscle responses to a change in treadmill frequency were significantly shorter at the posterior point for the gastrocnemius than for the tibialis anterior, and at the anterior point for the tibialis anterior than for the gastrocnemius. No correlated changes were seen in the corresponding head and joint movements. The difference in latency can best be attributed to the different body postures during the sinusoid. Early activation of the gastrocnemius is required due to the forward-directed impulse to the inclined body at the posterior point, and of the tibialis anterior muscle due to the backward-directed impulse to the erect body at the anterior point. It is suggested that afferent input from extensor load receptors provides information about the position of the body's centre of gravity relative to the support surface and determines the generation of the EMG responses. Adaptation of both the EMG and biomechanical patterns to a new sinusoidal frequency of the treadmill occurred within four cycles after the change. Biomechanically, this was reflected as a change in the body posture. Vision did not significantly affect these changes. In conclusion, standing on a sinusoidally moving platform, the nervous system acts to control the position of the body's centre of gravity relative to the feet. Body posture is adjusted in such a way that the forces acting on the body during the treadmill movements become minimised.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

[Goals of blood glucose regulation in prevention of diabetic retinopathy].

In several studies a correlation between blood glucose levels and HbA1 (A1c) and the prevalence of retinopathy was documented. Minimal risk for the onset of retinopathy was observed when HbA1 was below 9% from the beginning of diabetes mellitus. This HbA1 (A1c) value corresponds with values above 7 mmol of blood glucose. In intervention trials with near normal values of blood glucose, initially i.e. during the first months of treatment, an increase of microaneurysm was observed. However, in the next 7 years (as was observed in the Oslo Study) the grade of retinopathy in patients was less severe than in patients with HbA1 > 10%. Only 20% of patients treated conventionally can reach the aim of optimal blood glucose regulation. Obviously, in patients with diabetes beginning before the age of 30, this is the reason why the prevalence for the diabetic retinopathy is 40-98% after 15 years of diabetes. Only the functional insulin therapy allows the achievement of optimal blood glucose control in about 40% of patients without increased risk of hypoglycemia. Therefore, this kind of therapy should be the therapy of choice in a great number of type 1 diabetes patients.

Blood Glucose↗
PubMed1993

Stretch-induced electromyographic activity and torque in spastic elbow muscles. Differential modulation of reflex activity in passive and active motor tasks.

Stretch-evoked electromyographic (EMG) activity and torque signals have been studied in elbow joint muscles of both sides of patients with spastic hemiparesis and healthy subjects. In order to reveal differences in the generation of muscle tone between clinical assessment and functional movement, stretches of different velocities and amplitudes were applied during passive and quasi-functional active motor tasks. In spastic patients the strength and duration of the EMG responses following stretching of flexor and extensor muscles during both passive and active tasks were dependent on the stretch velocity and duration, respectively. This effect was seen on both the spastic and unaffected side. Under passive conditions EMG activity after stretching was negligible in the limb muscles of healthy subjects, of small amplitude in unaffected limbs of the patients, but was strong in affected muscles. Under active conditions, the amplitude of the early (M1) component of the EMG signal was larger, while the later components (M2 and M3) were smaller. These differences were due more to a change in reflex gain than to a change in reflex threshold when the stretch velocity signal was the basis for calculation. It is suggested that in spastic paresis, modulation of stretch-induced EMG activity in the spastic limb becomes restricted to a smaller range with a poor ability to switch off under passive conditions. Furthermore, the reflex EMG activity suffers a reduced facilitation under active conditions. In comparison with unaffected limbs the stretch-evoked torque on the affected side was increased under passive conditions (due to the extra EMG activity) and decreased under active conditions (due to a reduced EMG activity). An increased torque to EMG ratio was found in spastic flexor and extensor muscles during active tasks. This is thought to be due to changes in mechanical muscle fibre properties suffered as a consequence of defective muscle activation following cerebral lesions. The consequences for clinical assessment of muscle tone and therapy of spastic movement disorder are discussed.

Adult↗
PubMed1993

P-glycoprotein regulates chemosensitivity in early developmental stages of the mouse.

The multidrug resistance (MDR) P-glycoprotein (P-gp) is an active transporter associated with chemoresistance of tumor cells. A fundamental aspect not yet entirely clarified is the physiological role of MDR-P-gp in normal mammalian tissues. In this paper we report that multidrug (chemo)resistance is already present in mouse oocytes and early cleavage embryos. Expression of MDR-specific P-gp is detectable by antibody (C219) staining from the primary oocyte onward to the eight-cell embryo. MDR-mRNA is demonstrated in mature oocytes using an Mdr1-specific cDNA probe. Functional activity of P-gp is shown by the efficacy of MDR reversers (verapamil or quinidine) in enhancement of: 1) drug accumulation (daunomycin) in all stages investigated, 2) drug cytotoxicity (daunomycin or mitomycin c-induced developmental impairment) in two-cell embryos cultured for 24 h, and 3) drug cytokinesis-blocking activity (cytochalasin D; our recent findings demonstrate cytochalasins to be substrates for P-gp and to indicate the presence of MDR by their microfilament-disrupting action on cycling cells) in four- and eight-cell embryos cultured for 24 h. Furthermore, functional involvement of P-gp in vivo is demonstrated. Concurrent administration of verapamil increases doxorubicin-induced developmental impairment in the zygote stage during the first cleavage cycle in pregnant females. Results provide evidence that MDR-P-gp has an efficient protective function in early reproduction.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Treatment of early-morning hyperglycemia in type 1 diabetics with amorphous zinc insulin (Semilente) at bedtime.

Fasting hyperglycemia in insulin-dependent diabetic patients (IDDM) treated according to the basal-bolus principle may be due to the fact that currently available neutral protamine Hagedorn (NPH) insulin preparations do not sufficiently meet the increased insulin need in the second part of the night. In the present study, it was investigated whether the amorphous zinc insulin Semilente can be used to control fasting hyperglycemia in IDDM patients. Ten type 1 diabetic patients with persistent fasting hyperglycemia (> 10 mmol/l) participated in the double-blind randomized cross-over trial with 2 10-day treatment periods. Night profiles of blood glucose and free insulin concentrations were determined at the end of each treatment period. Three doses of regular insulin were given before the meals and NPH insulin and Semilente at 10.00 p.m. Nighttime blood glucose and insulin profiles were different under the treatment with Semilente and NPH insulin. Injection of Semilente at bedtime resulted in higher insulin and lower blood glucose values during the second part of the night (p < 0.001 versus Semilente by ANOVA). Semilente injected at bedtime can prevent the early-morning rise in blood glucose in type I diabetic patients.

Adult↗
PubMed1993

Middle cerebral artery blood flow velocity in healthy persons during wakefulness and sleep: a transcranial Doppler study.

In 10 normal young adults, middle cerebral artery blood flow velocity was measured continuously over one night by transcranial Doppler sonography. Polysomnography was used to assess the different sleep stages and waking state. During rapid eye movement (REM) sleep, middle cerebral artery blood flow velocity was higher than in any other sleep stage and wakefulness. During the waking state the velocity was higher than in sleep stage 2. Spontaneous rhythmic oscillations of cerebral blood flow velocity were found related to different stages of sleep. A fast Fourier's transformation of the Doppler wave forms revealed a periodicity of 20-75 seconds, which was most prominent during REM sleep and to a lesser degree during sleep stages 1, 2 and 3 and the waking state. These waves may correspond to intracranial pressure changes referred to as B-waves.

Adult↗
PubMed1992

Generation and characterization of radiation reduced cell hybrids and isolation of probes from the proximal short arm of the human X chromosome.

Employing a modified Goss-Harris irradiation fusion protocol, we have generated a panel of somatic cell hybrids containing various overlapping fragments of the Xcen-Xp11.4 interval. This region of the human X chromosome is known to carry genes for several hereditary eye diseases including retinitis pigmentosa (RP2), congenital stationary night blindness (CSNB-1) and Norrie disease. These hybrid cell lines were employed to isolate 17 new DNA probes by making use of the Alu polymerase chain reaction (PCR) method and subsequent cloning of the PCR products in a plasmid vector. With these probes, we have characterized two previously described microdeletions spanning the Norrie locus; these deletions have enabled us to subdivide the Xp11.4-p11.3 region into three defined intervals.

Animals↗
PubMed1992

Developmental aspects of stance regulation, compensation and adaptation.

Recordings of electromyographic (EMG) leg muscle activity, head and joint movements and platform torque were taken in healthy subjects within three age groups (approximately 6, 10 and greater than 22 years) standing upright upon a sinusoidally moving treadmill. The sinusoidal frequency was randomly changed between 0.5, 0.33 and 0.25 Hz, while the amplitude of the deflection was constant (+/- 12 cm). During an adapted sinus, forward inclination of the body at the posterior turning point was associated with a slowly increasing tibialis anterior and decreasing gastrocnemius activity, while straightening of the body at the anterior turning point was associated with a sharply increasing gastrocnemius and decreasing tibialis anterior activity. The angle of forward inclination was greatest in the groups of children and was dependent upon both the sinus frequency and the child's height. The presumed programmed adjustment of the body inclination was such that the net effect of both inertial and gravitational forces acting on the body coincided approximately with the axis of the body at the posterior turning point. Changes of sinusoidal frequency were followed by compensatory responses, the amplitude of which depended upon the velocity of the body's displacement and the height of the subjects. In all three subject groups the response latencies were significantly shorter at the posterior turning point for the gastrocnemius response to a change from 0.5 to 0.25 Hz (105 ms for children and 119 ms for adults) than for the tibialis anterior response to a change from 0.25 to 0.5 Hz for which the values were 162 and 169 ms, respectively. This difference could be attributed to the forward inclination of the body at the posterior turning point which requires an earlier onset of compensatory extensor activity in order to maintain equilibrium. Adaptation to a new sinusoidal frequency occurred within 4 cycles following a change in sinus frequency. The phase shifts between treadmill position and the biomechanical and EMG signals that occurred during the adaptational process suggest that the position of the body's centre of gravity is the variable controlled by the programmed leg muscle activation. In young children the phase shifts during adaptation were absent, which may contribute to their greater instability. It is concluded that posture is continually adjusted in such a way that the resulting torque acting on the body during the treadmill movement becomes minimized. For this regulation load receptors in addition to the classical afferent impulses from visual, vestibular and muscle stretch receptors could play a major role.

Acclimatization↗
PubMed1992

Alzheimer's disease: is the decrease of the cholinergic innervation of the hippocampus related to intrinsic hippocampal pathology?

Consistent findings in the hippocampi of patients with Alzheimer's disease are the presence of neurofibrillary tangles in pyramidal neurons and the loss of choline acetyltransferase activity due to degeneration of hippocampal cholinergic terminals. The present study sought to clarify, in the brains of five patients with Alzheimer's disease and four controls, whether the loss of cholinergic terminals in the hippocampal stratum pyramidale in Alzheimer's disease is related to degenerative changes in hippocampal pyramidal cells. A polyclonal antibody to human choline acetyltransferase was employed to visualize immunohistochemically cholinergic terminals. Hippocampal neurons were stained with Cresyl Violet, neurofibrillary tangles with thioflavin S and a monoclonal antibody against phosphorylated neurofilament (RT97). Quantification of the stained structures was performed in CA4, CA1 and the subiculum, on five sections selected from the entire anteroposterior extent of each hippocampus. In the group of Alzheimer patients, the densities of cholinergic terminals were homogeneously diminished in the three hippocampal subregions in comparison with the controls (32-33%). In contrast, a significant loss of pyramidal neurons was found only in CA1, and the density of neurofibrillary tangles was markedly increased only in CA1 and the subiculum in Alzheimer's disease. These findings suggest that there is no relationship between the loss of cholinergic terminals and the degeneration of pyramidal cells in the hippocampus of patients with Alzheimer's disease.

Aged↗
PubMed1992

Treatment of diabetic ketoacidosis and non-ketotic hyperosmolar diabetic coma.

Although mortality of diabetic ketoacidosis (KA) has decreased during the past 20 yr to 1-2%, hyperosmolar non-ketotic coma (HNC) is still lethal in 20-30% of cases due to severe underlying conditions or to complications. The most frequent causes of death are infections and thromboembolic disorders. The strategies of initial treatment of KA and HNC are similar; in KA, insulin, fluid and electrolyte replacement have first priority. In HNC, rehydration and electrolyte administration are of primary importance. It is now generally recognized that insulin therapy is best performed using low doses (4-8 units/h); after institution of insulin treatment and rehydration there are rapid changes of fluid and electrolytes from the extra- into the intravascular space. In this situation it is a major therapeutic challenge to avoid complications due to hypokalaemia, hypophosphataemia, hypomagnesaemia and hypovolaemia. These complications should be avoided by adequate replacement, and particularly by regular clinical and laboratory monitoring. When blood glucose concentrations decrease below 14 mmols/l, blood glucose concentrations should initially be maintained at this level because rapid lowering below this level may increase the risk of brain oedema. Too-vigorous fluid replacement with crystalline solutions also increases the risk that brain oedema or complications like the adult respiratory distress syndrome will develop. If hypovolaemia persists in spite of adequate crystalloid solutions, colloid-containing fluids such as albumin should be administered. It is not established whether replacements of phosphate and magnesium have clinical benefits. Nevertheless, it is probably justified to administer phosphate and magnesium when their serum concentrations are below the normal range, particularly if the clinical situation is critical. Mortality from diabetic coma in industrialized countries may only be decreased by prophylaxis, i.e. by education of all diabetic patients and physicians to detect metabolic decompensation early.

Diabetic Coma↗
PubMed1992

Isolation of a candidate gene for Norrie disease by positional cloning.

The gene for Norrie disease, an X-linked disorder characterized by progressive atrophy of the eyes, mental disturbances and deafness, has been mapped to chromosome Xp11.4 close to DXS7 and the monoamine oxidase (MAO) genes. By subcloning a YAC with a 640 kilobases (kb) insert which spans the DXS7-MAOB interval we have generated a cosmid contig which extends 250 kb beyond the MAOB gene. With one of these cosmids, microdeletions were detected in several patients with Norrie disease. Screening of cDNA libraries has enabled us to isolate and sequence a likely candidate gene for Norrie disease which is expressed in retina, choroid and fetal brain. No homologous sequences were found in DNA and protein databases indicating that this cDNA is part of a gene encoding a 'pioneer' protein.

Adult↗
PubMed1992

Norrie disease is caused by mutations in an extracellular protein resembling C-terminal globular domain of mucins.

A candidate gene for Norrie disease, an X-linked disorder characterized by blindness, deafness and mental disturbances, was recently isolated and found to contain microdeletions in numerous patients. No strong homologies were identified. By studying the number and spacing of cysteine residues, we now detect homologies between the Norrie gene product and a C-terminal domain which is common to a group of proteins including mucins. Three newly-characterized missense mutations, replacing evolutionarily conserved cysteines or creating new cysteine codons, emphasize the functional importance of these sites. These findings and the clinical features of this disorder suggest a possible role for the Norrie gene in neuroectodermal cell-cell interaction.

Adult↗