Biomedical subjects

P Zimmermann

Publications and source records attributed to P Zimmermann.

At least 19 recordsLinked to original sources

PubMed1995

Doppler flow velocimetry of the umbilical artery, uteroplacental arteries and fetal middle cerebral artery in prolonged pregnancy.

A total of 153 pregnant women, of at least 287 days' menstrual age, were studied in a prospectively designed cross-sectional trial. In addition to the non-stress test, contraction stress test, sonographic estimate of amniotic fluid and grade of placental maturation, Doppler measurements of the resistance index (RI) were taken in the umbilical artery, the uteroplacental arteries in the region of placental implantation and the fetal middle cerebral artery. Data were analyzed with regard to asphyxia and otherwise complicated fetal outcome. Furthermore, a possible relationship between grade of placental maturation, Doppler flow velocity waveforms and fetal outcome was investigated. Doppler resistance indices in the umbilical artery, uteroplacental arteries in the region of placental implantation and fetal middle cerebral artery did not change significantly with increasing gestation from 41 to 43 weeks. The grade of placental maturation on ultrasound examination was not related to fetal outcome or Doppler indices in the first two vessels. In all vessels examined in this study, the majority of Doppler measurements in pregnancies with subsequent asphyxia or otherwise complicated fetal outcome were within the 95% prediction interval for patients with normal fetal outcome. None of the patients showed absent diastolic flow in the umbilical artery. With the use of a cut-off value of RI = 0.62 in the umbilical artery, asphyxia could be predicted with 37% sensitivity and 75% specificity. Oligohydramnios and antpartum cardiotocography predicted asphyxia with 16% and 8% sensitivity and 95% and 96% specificity, respectively. Sensitivity for prediction of otherwise complicated fetal outcome by umbilical artery Doppler was only 7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗

PubMed1995

Thermal threshold determination in alcoholic polyneuropathy: an improvement of diagnosis.

Reports on the incidence of alcoholic polyneuropathies are variable depending on diagnostic tools. In this study, 50 chronic alcoholics with positive MALT (Munich Alcoholism Test) and greater than seven years history of excessive alcohol abuse were examined neurologically. Tibial and peroneal motor and sural nerve conduction velocities (NCV) were studied. Warm and cold perception was evaluated in the area behind the internal malleolus using a Somedic-Thermotest. Thresholds were determined by the method of limits. The effect of a slow, medium and fast temperature change rate on thermal perception was tested. Thirty-eight patients (76%) showed signs of neuropathy. Thermal perception was more often abnormal (62%) than NCV (42%) and clinical examination (56%). A medium temperature change rate of 2.0-2.5 degrees C/s was the most sensitive index of small fiber neuropathy. Thermal threshold measurement proved to be a reliable, sensitive and easy to perform method that should become standard in the examination of polyneuropathies.

Adult↗

PubMed1994

Incomplete split-brain syndrome in a patient with chronic Marchiafava-Bignami disease.

A 40-year-old male patient is presented who survived Marchiafava-Bignami disease and recovered sufficiently to be assessed neurologically and neuropsychologically in some detail. Besides dementia, lack of initiative, and psychomotor retardation here ascribed to extracallosal damage, he showed a number of symptoms of hemispheric disconnection such as left-sided apraxia, poor bimanual coordination in specific laboratory tests, and deficits in the interhemispheric transfer of somaesthetic information. Other commissural functions, such as interhemispheric transfer of tactile, visual and auditory information as well as bilateral coordination in previously overlearned tasks, were nearly intact. The observed dysarthria could be meaningfully discussed in relationship to postcallosotomy mutism. It is concluded, that the partial interhemispheric disconnection syndrome in Marchiafava-Bignami disease lacks functional compensation which is different from the usual course in partial commissural section.

Adult↗

PubMed1994

Different mechanisms underly shifting set on external and internal cues in Parkinson's disease.

A set shifting task consisting of the comparison of two digits according to their numerical value or their form guided by an explicit (external cue) or implicit (internal cue) rule was performed by 8 untreated and 19 treated patients suffering from Parkinson's disease (PD) and 15 control subjects. The subjects could not predict the number of trials for a given target. The treated PD patient group exhibited increased post-shift error rates under the internal cue condition. In the external cue condition, only the untreated patients produced more errors when shifting to a new response criterion. Reaction times were prolonged in treated PD patients, irrespective of type of cue. Large interindividual variability within the patient groups is considered as meaningful and indicates individual differences in the neuropsychological impairment and/or the neurotransmission deficit. Pathophysiological and neuropsychological impairments underlying these findings are discussed on the basis of the models of Penney and Young (1983/1986) and Norman and Shallice (1980/1986).

Aged↗

PubMed1992

Doppler velocimetry of the umbilical artery in pregnancies complicated by insulin-dependent diabetes mellitus.

The purpose of this study was to investigate vascular resistance by Doppler ultrasound in the umbilical artery of insulin-dependent diabetics longitudinally over the course of pregnancy. Special interest was put on the effects of glycemic control and maternal vascular disease on the flow velocity waveform (FVW) and the predictive value of Doppler flow measurements with regard to perinatal morbidity. Using a duplex-pulsed wave scanner, the resistance-index (PR index) in the umbilical artery was calculated. The mean value of a 24-h blood glucose profile and the concentration of glycosylated hemoglobin (HBA1C) were used as parameters of metabolic control. 53 pregnant diabetic women were examined longitudinally during the course of pregnancy on average on three occasions (range: 1-7) between 17 weeks of gestation and delivery at 37.7 +/- 1.3 (mean +/- SD) weeks. To test the predictive value of Doppler flow velocimetry with regard to perinatal morbidity the results were compared to the FVWs measured in the umbilical arteries of 30 non-diabetic women with normal fetal outcome. Vascular resistance in the umbilical artery of the diabetics declined significantly during the course of pregnancy, with a mean PR index of 0.729 (SD 0.051) at 17 weeks and 0.603 (SD 0.083) at the end of pregnancy (P < 0.002). The majority of PR indices were within the range reported for normal pregnancy and measured in the non-diabetic women. Regression analysis showed no significant correlation between vascular resistance and mean blood glucose level (r = 0.1325) or concentration of HBA1C (r = -0.0519). Maternal vascular disease had no effect on umbilical FVWs.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 1↗

PubMed1992

Modified structure and kinetics of cytochrome-c oxidase in fibroblasts from patients with Leigh syndrome.

In this study we compared the properties of cytochrome-c oxidase (COX) in cultured fibroblasts from two patients with Leigh Syndrome with COX from control fibroblasts. The fibroblasts from patients showed decreased growth rates and elevated lactate production. COX activity of patients fibroblasts was about 25% of control. Kinetic studies with isolated mitochondria showed a higher Km for cytochrome c and a markedly reduced molecular turnover of COX from patients, indicating a different structure of the enzyme. A biphasic change of COX activity was obtained by titration of dodecylmaltoside solubilized mitochondria from control fibroblasts with increasing concentrations of anions. With patient mitochondria we found only the inhibiting phase of COX activity and, in contrast to control mitochondria, irreversible inhibition of COX activity by guanidinium chloride. ELISA titrations with monoclonal antibodies to subunit II, IV, Vab, Vlac and VIIab indicated a normal amount of mitochondrial coded subunit II, but a reduced amount of nuclear coded subunits. The data indicate incompletely assembled nuclear coded subunits of COX from patient fibroblasts.

Blotting, Western↗

PubMed1992

Intravesicular acidification correlates with binding of ADP-ribosylation factor to microsomal membranes.

The ADP-ribosylation factor (ARF), a highly conserved low molecular weight GTP-binding protein, has been implicated to function in intracellular protein transport to and within the Golgi complex. In pancreatic acinar cells the ARF is confined to the cytoplasmic faces of trans-Golgi stack membranes, a compartment known to maintain a low intravesicular pH, which is established by a chloride-dependent MgATP-driven proton pump. The present study shows that MgATP (2mM), but neither adenosine 5'-[gamma-thio]triphosphate in the presence of Mg2+ nor ATP in the absence of Mg2+, increases transfer of ARF from the surrounding medium into the vesicle membranes. The specific vacuolar-type proton pump inhibitor bafilomycin B1 (10 nM), the protonophore carbonylcyanide m-chlorophenylhydrazone (10 microM), and replacement of chloride in the incubation buffer by acetate or nitrate resulted in an almost complete inhibition of the MgATP-dependent association of ARF to the vesicle membranes. The results demonstrate that redistribution of ARF to the vesicle membrane correlates with the intravesicular pH established by a vacuolar-type H(+)-ATPase. The intravesicular pH appears to be one mechanism by which certain low molecular weight GTP-binding proteins become relocated from the cytosol to their specific membrane vesicles.

ADP-Ribosylation Factors↗

PubMed1992

Association of a 19- and a 21-kDa GTP-binding protein to pancreatic microsomal vesicles is regulated by the intravesicular pH established by a vacuolar-type H(+)-ATPase.

Evidence suggests that certain ras-related small molecular weight GTP-binding proteins (smg-proteins) are involved in intracellular membrane trafficking and vesicle fusion. We have previously shown that intravesicular acidification due to a vacuolar-type H(+)-ATPase, which is Cl- dependent and highly sensitive to the specific inhibitor bafilomycin, enhances GTP-induced fusion of pancreatic microsomal vesicles (Hampe, W., Zimmermann, P., Schulz, I. 1990. FEBS Lett. 271:62-66). This process may involve function of smg-proteins. The present study shows that MgATP (2 mM), but neither MgATP gamma S nor ATP in the absence of Mg2+, increases association of 19- and 21-kDa smg-proteins to the vesicle membrane as monitored by their [ alpha-32P]GTP binding. The affinity of smg-proteins for [ alpha-32P]GTP was not altered by MgATP. Bafilomycin B1 (10(-8) M), the protonophore CCCP (10(-5) M), and replacement of Cl- in the incubation buffer by CH3COO- or NO3- resulted in an almost complete inhibition of the MgATP-dependent association of the 19- and 21-kDa smg-proteins to the vesicle membranes. Furthermore, the MgATP effect on both smg-proteins was found to be due to the intravesicular pH and not to the H+ gradient over the vesicle membrane. We conclude that association of a 19-kDa (immunologically identified as the ADP-ribosylation factor, arf) and a yet unidentified 21-kDa GTP-binding protein to vesicle membranes is regulated by the intravesicular pH established by a vacuolar-type H(+)-ATPase.

Adenosine Triphosphate↗

PubMed1992

Cognitive slowing in decision tasks in early and advanced Parkinson's disease.

Ten untreated patients with recently diagnosed Parkinson's disease (PD), 9 treated patients with more advanced pathology, and 17 matched normal controls were investigated with three reaction tasks with increasing cognitive load but identical motor requirements: simple reaction, choice reaction with indicative stimuli, and choice reaction with ambiguous stimuli. Times required until a home key was released (= reaction time) and from then until a response key was pressed (= movement time) were recorded. Estimates of pure decision time (overall response time minus movement time in a simple reaction time task) revealed a difference between advanced and early PD patients. Advanced PD patients showed an overall slowing of decision time in the reaction time tasks, but the effect of the cognitive load of the tasks on the decision time was comparable to a control group. The untreated early PD patients performed quite normally in the more simple decision tasks but showed a disproportionate slowing of decision time in tasks with higher cognitive load.

Adult↗

PubMed1992

Bombesin receptors interact with Gi and p21ras proteins in plasma membranes from rat pancreatic acinar cells.

This study investigates interaction of bombesin receptors with heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) and monomeric small molecular weight GTP-binding proteins (smg proteins), respectively, in plasma membranes (PM) of rat pancreatic acinar cells. Addition of bombesin to isolated PM stimulated the incorporation of the photoaffinity analogue [alpha-32P]GTP-gamma-azidoanilide into Gi proteins of 40-41 kDa and reduced the pertussis toxin-induced ADP ribosylation of three 40-41 kDa proteins, which had been previously identified as Gi1, Gi2, and Gi3 (30). In PM isolated from bombesin-prestimulated acinar cells, binding of [alpha-32P]-GTP to PM proteins of 21-22 kDa and of a monoclonal antibody against p21ras proteins was increased. Two-dimensional separation of PM proteins revealed the presence of 18 or 19 differently charged smg proteins. The p21ras proteins could be separated into two differently charged proteins with isoelectric points of 5.58 and 5.79. In microsomal membranes (MM), [alpha-32P]GTP binding to yet unidentified 21-22 kDa smg proteins was decreased compared with membranes from unstimulated acinar cells. The data suggest that Gi proteins as well as p21ras proteins are involved in bombesin receptor-mediated signal transduction in the PM. Furthermore, 21-22 kDa smg proteins in MM might play a role in bombesin-induced stimulation of intracellular pathways that lead to enzyme secretion from pancreatic acinar cells.

Affinity Labels↗

PubMed1992

Effects of agonists on p21ras and ras-related proteins in rat pancreatic acinar cells.

This study shows the presence of seven different low-molecular-weight GTP binding proteins (smg proteins) with molecular masses between 18 and 27 kDa in subfractions of rat pancreatic acinar cells. After stimulation of isolated intact and permeabilized pancreatic acinar cells with cholecystokinin octapeptide (CCK-OP), the diacylglycerol (DG) analogue 12-O-tetradecanoylphorbol 13-acetate (TPA), vasoactive intestinal peptide (VIP), adenosine 3',5'-cyclic monophosphate (cAMP), or guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), [alpha-32P]GTP binding to 21- to 22-kDa smg protein(s) in microsomal membranes (MM) was reduced, whereas the [alpha-32P]GTP binding to 23-kDa protein(s) was enhanced. In addition, prestimulation of permeabilized cells with GTP gamma S caused enhancement of [alpha-32P]GTP binding to a 19-kDa protein in MM [immunologically identified as the ADP-ribosylation factor (arf)]. In the presence of cytosol, direct addition of GTP gamma S to isolated MM resulted in an apparent translocation of the 19-kDa protein (arf) from the cytosol to membranes. This indicates increased association of arf with the membrane in its GTP-bound state. In CCK-OP-prestimulated acinar cells, [alpha-32P]GTP binding to plasma membrane-located 21- to 22-kDa proteins (immunologically identified as p21ras proteins) was enhanced, suggesting that there is an interrelationship between p21ras proteins and CCK receptors. Our results give evidence for a role of 19-kDa, 21- to 22-kDa, and 23-kDa smg proteins in cAMP-protein kinase A- and DG-protein kinase C-mediated stimulation of intracellular pathways in pancreatic acinar cells.

Animals↗

PubMed1992

[The effect of fluoridated milk on caries reduction over 12 years].

The aim of the study was to assess the caries-preventive effect of fluoridated milk after 12-years of consumption, including 2 years interruption. DMF mean values of 162 institutionalized children aged 7-to 14 years were compared with DMF mean values of 139 institutionalized control children of the same age. The children consumed 200 ml milk daily, implemented with 0.4 mg -0.75 mg F(-)--depending on their age--between 1979-1984, after 2 years interruption they got fluoridated milk or cocoa-milk twice a week during 10 years. In the test group the ratio of caries-free children averaged more than 10%. The caries prevalence in the permanent dentition showed statistically significant reduction. The caries reduction regarding all groups was 36.78% in case of DMF-T, and 40.02% of DMF-S. According to our results the consumption of fluoridated milk in institutionalized children proved to be effective also in the long run.

Adolescent↗

PubMed1992

Effect of fluoridated milk on caries: 10-year results.

The aim of the study was to assess the caries-preventive effect of fluoridated milk after 10 years of consumption, including a two-year interruption. DMF mean values of 162 institutionalized children aged 7- to 14-years were compared to DMF mean values of 139 institutionalized children (control) of the same age. The test group children consumed 200 ml milk daily, implemented with 0.4 mg-to 0.75 mg F, depending on their age, continuously for six years. Following a two year interruption, the children again got fluoridated milk or cocoa-milk twice a week for four years. In the test group the average ratio of caries-free children was 10% more than in the control group. The caries prevalence in the permanent dentition showed a clinically and statistically significant reduction: 36.78% on DMFT, and 40.02% on DMFS mean values.

Adolescent↗

PubMed1992

[Gastric metastases. Apropos of 17 cases].

Seventeen cases of gastric metastases are reported; some of them appeared after a long latency period. Two cancers prevail from an aetiological standpoint: melanoma (7 cases) and breast cancer (4 cases). Endoscopic appearance is often typical in melanoma, but suggests a primary carcinoma or radiation-induced lesions in breast cancer. Surgery is reserved to located lesions, but seems to have no incidence on prognosis. Overall mean survival is 11 months with a range of 3 months to 5 years.

Adult↗

PubMed1991

Guanosine nucleotides modulate the inhibitory effect of brefeldin A on protein secretion.

Brefeldin A (BFA) causes rapid redistribution of Golgi proteins into the endoplasmic reticulum (ER), leaving no definable Golgi-apparatus, and blocks transport of proteins from the ER to distal secretory compartments of the cell. Using pulse-chase experiments the present study shows that BFA (1 microgram/ml) inhibits basal and CCK-stimulated protein secretion in isolated pancreatic acinar cells by 65 +/- 6% and 84 +/- 5%, respectively. In isolated permeabilized cells higher concentrations of BFA (30 micrograms/ml) were necessary to obtain inhibition of protein secretion. In parallel experiments protein secretion was stimulated by GTP (1 mM). BFA had no inhibitory effect on protein secretion in the presence of GTP, indicating that BFA might act on a GTP-binding protein. Investigating the effect of BFA on small molecular weight GTP-binding proteins we observed that [alpha-32P]GTP binding to a 21 kDa protein in a subcellular fraction enriched in ER was increased in the presence of BFA. We conclude that this 21 kDa and possibly also other GTP-binding proteins may be the molecular target of Brefeldin A in pancreatic acinar cells.

Animals↗

PubMed1991

Prevention of bleomycin-induced fibrosing alveolitis with indomethacin: stereological studies on rat lungs.

The prevention of the pulmonary toxicity of bleomycin (BLM) has been investigated in experimental models where pulmonary damage was induced with one intra-tracheal dose of BLM. The present investigation was carried out as a pre-clinical study in which BLM was administered systemically. The non-steroid anti-inflammatory drug indomethacin (INDO) was chosen as a possible candidate for pulmonary protection. Twenty female Wistar rats were treated daily with 4 mg/kg (7.3 units) BLM intra-peritoneally for 50 days and 20 rats with BLM and with 1 mg/kg INDO subcutaneously for 62 days. There were 20 animals as controls. Histological examination revealed fibrosing alveolitis in the BLM-treated group which was markedly suppressed in the combination group. Quantitative morphological (stereological) parameters demonstrate that BLM induced alveolar wall thickening (+45%), pulmonary fibrosis (+110%), and an increase of alveolar wall nuclei and of intra-alveolar macrophages (volume densities +43% and +133%, P less than 0.001). In contrast, after combination with INDO significant differences to the control group could not be detected except for a slight increase of intra-alveolar macrophages (+62%). Thus, INDO is a highly efficient agent in the prevention of BLM-induced pulmonary damage.

Animals↗

PubMed1991

Mental planning and anticipatory processes with acute and chronic frontal lobe lesions: a comparison of maze performance in routine and non-routine situations.

A series of computerized mazes were masked during presentation allowing only partial view of their structure. Patients suffering from acute or chronic unilateral frontal (medial, lateral) or retrorolandic (temporal, parietal) lesions and non-brain-damaged controls were required to pass through the mazes repeatedly, until they solved them without reaching a dead end. Because the mazes could not be viewed in their entirety at any one time, the subjects were forced to mentally generate and apply a plan of the maze. The first ("non-routine" situation), the second and the last ("routine" situation) trials of the mazes were analysed separately. The prefrontal cortex is supposed to subserve important functions in the planning of behaviour in unfamiliar, non-routine situations. Shallice (Phil. Trans. R. Soc. Lond. B298, 199-209, 1982; From Neuropsychology to Mental Structure, Cambridge University Press, Cambridge, 1988) therefore postulated that the behaviour of patients with frontal lobe lesions should not be disturbed in routine situations, but rather these patients should exhibit difficulties in dealing with new and unfamiliar situations. In the present investigation, patients with acute and chronic frontomedial lesions exhibited deficits in generating mental plans. Patients with acute frontomedial lesions made a larger number of errors in their second trials and subsequently required more trials to reach task criterium. Patients with chronic frontomedial lesions showed more frequent rule-breaking behaviour in their second trials. The analysis of maze performance in the first trial and that trial in which task criterion was achieved, showed that frontal lobe patients were impaired in neither routine nor non-routine situations. The observed results suggest a modification concerning Shallice's assumptions. Patients with frontomedial lesions are not generally incapable of dealing with non-routine situations. But they seem to be slower than patients with retrorolandic lesions and controls in profiting from experiences made in an unfamiliar, non-routine situation represented by the first explorations of new maze problems. This deficit can possibly be explained by the observation that anticipatory processes or the formation of expectations about possibly correct decisions in non-routine situations were altered in acute and chronic frontomedial patients. When these patients reached a maze intersection for the first time and therefore had no information about the continuation of the correct path, they showed significantly different intuitive directional decisions when compared to controls.

Adult↗

PubMed1991

Doppler umbilical artery velocimetry in pregnancies complicated by intrahepatic cholestasis.

Doppler umbilical velocimetry is a useful clinical tool for antepartum fetal surveillance of pregnancies at risk of fetal compromise. Intrahepatic cholestasis of pregnancy is associated with an increased incidence of fetal death, which might due to the toxic effect of elevated maternal serum concentrations of bile acids. To study a possible effect of the concentration of bile acids on the umbilical circulation we performed pulse-wave Doppler velocimetry of the umbilical artery in 15 patients with intrahepatic cholestasis between 34 and 38 weeks of gestation. The findings were compared to the Doppler flow velocities of the umbilical artery of 129 normal pregnancies. Peak-systolic (A) and end-diastolic (B) velocities of two to three cardiac cycles were measured by electronic calipers and the Pourcelot (PR)-index (PR = (A - B)(A)) was calculated. Two of 29 Doppler measurements in patients with intrahepatic cholestasis were above two standard deviations (2 SD) of the values in normal pregnancies. No significant correlation was found between Doppler flow velocities and serum levels of bile acids (r = 0.20) or the levels of alanine aminotransferase (ALAT) (r = -0.05). The mean level of bile acids was 24 mumol/l with a maximum of 98 mumol/l. The mean level of ALAT was 165 IU/l with a maximum of 576 IU/l. Since even high levels of bile acids do not influence umbilical circulation, Doppler investigations of the umbilical artery seem to be of little value in studying the disease-specific risk of fetal compromise in pregnancies complicated by intrahepatic cholestasis.

Alanine Transaminase↗