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Biomedical subjects

H Schulz

Publications and source records attributed to H Schulz.

At least 19 recordsLinked to original sources
PubMed1998

Prototype of a heme chaperone essential for cytochrome c maturation.

Heme, the iron-containing cofactor essential for the activity of many enzymes, is incorporated into its target proteins by unknown mechanisms. Here, an Escherichia coli hemoprotein, CcmE, was shown to bind heme in the bacterial periplasm by way of a single covalent bond to a histidine. The heme was then released and delivered to apocytochrome c. Thus, CcmE can be viewed as a heme chaperone guiding heme to its appropriate biological partner and preventing illegitimate complex formation.

Amino Acid Sequence↗
PubMed1998

A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in Alzheimer's disease.

A novel L-3-hydroxyacyl-CoA dehydrogenase from human brain has been cloned, expressed, purified, and characterized. This enzyme is a homotetramer with a molecular mass of 108 kDa. Its subunit consists of 261 amino acid residues and has structural features characteristic of short chain dehydrogenases. It was found that the amino acid sequence of this human brain enzyme is identical to that of an endoplasmic reticulum amyloid beta-peptide-binding protein (ERAB), which mediates neurotoxicity in Alzheimer's disease (Yan, S. D., Fu, J., Soto, C., Chen, X., Zhu, H., Al-Mohanna, F., Collison, K., Zhu, A., Stern, E., Saido, T., Tohyama, M., Ogawa, S., Roher, A., and Stern, D. (1997) Nature 389, 689-695). The purification of human brain short chain L-3-hydroxyacyl-CoA dehydrogenase made it possible to characterize the structural and catalytic properties of ERAB. This NAD+-dependent dehydrogenase catalyzes the reversible oxidation of L-3-hydroxyacyl-CoAs to form 3-ketoacyl-CoAs, but it does not act on the D-isomers. The catalytic rate constant of the purified enzyme was estimated to be 37 s-1 with apparent Km values of 89 and 20 microM for acetoacetyl-CoA and NADH, respectively. The activity ratio of this enzyme for substrates with chain lengths of C4, C8, and C16 was approximately 1:2:2. The human short chain L-3-hydroxyacyl-CoA dehydrogenase gene is organized into six exons and five introns and maps to chromosome Xp11.2. The amino-terminal NAD-binding region of the dehydrogenase is encoded by the first three exons, whereas the other exons code for the carboxyl-terminal substrate-binding region harboring putative catalytic residues. The results of this study lead to the conclusion that ERAB involved in neuronal dysfunction is encoded by the human short chain L-3-hydroxyacyl-CoA dehydrogenase gene.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1998

Significance of the reductase-dependent pathway for the beta-oxidation of unsaturated fatty acids with odd-numbered double bonds. Mitochondrial metabolism of 2-trans-5-cis-octadienoyl-CoA.

The beta-oxidation of unsaturated fatty acids with odd-numbered double bonds proceeds by reduction of the double bond (reductase-dependent pathway) in addition to the well established isomerization of the double bond (isomerase-dependent pathway). The metabolic significance of the reductase-dependent pathway was assessed with 2-trans-5-cis-octadienoyl-CoA (2,5-octadienoyl-CoA) and its products, all of which are metabolites of alpha-linolenic acid. A kinetic evaluation of beta-oxidation enzymes revealed that the presence of a 5-cis double bond in the substrate most adversely affected the activity of 3-ketoacyl-CoA thiolase although not enough to become rate-limiting. Concentration-dependent and time-dependent measurements indicated that most (80%) of 2,5-octadienoyl-CoA is metabolized via the isomerase-dependent pathway. The reason for the greater flux through the isomerase-dependent pathway is the higher activity of L-3-hydroxyacyl-CoA dehydrogenase as compared with Delta3,Delta2-enoyl-CoA isomerase. These two enzymes catalyze the rate-limiting steps in the isomerase-dependent and reductase-dependent pathways, respectively. Once 2,5-octadienoyl-CoA is converted to 3,5-octadienoyl-CoA (perhaps fortuitously because of the presence of Delta3,Delta2-enoyl-CoA isomerase), the only effective route for its degradation is via the reductase-dependent pathway. It is concluded that the reductase-dependent pathway assures the degradation of 3,5-dienoyl-CoA intermediates, thereby preventing the depletion of free coenzyme A and a likely impairment of mitochondrial oxidative function.

Acyl Coenzyme A↗
PubMed1998

Long-term effectiveness of a new alpha-glucosidase inhibitor (BAY m1099-miglitol) in insulin-treated type 2 diabetes mellitus.

In a double-blind, randomized study, miglitol (BAY m 1099), an alpha-glucosidase inhibitor, 100 mg tds or placebo was given orally with meals for a period of 24 weeks in 117 patients with Type 2 (non-insulin-dependent) diabetes mellitus (DM) treated with insulin. Fasting and 1 h postprandial plasma glucose and C-peptide were measured at the beginning and at the end of each 4-week interval and glycosylated haemoglobin was determined at day 0 and at the end of the 12th and 24th week. One hour postprandial plasma glucose was significantly lower in the miglitol group at the end of the 24th week (placebo: 11.6 +/- 1.5 vs miglitol: 8.2 +/- 1.5 mmol l-1, mean +/- SD, p = 0.001). Diabetes control improved in the same group as the HbA1 was lowered by 16% (p = < 0.0001) at the end of the treatment. Mild reversible adverse effects were observed in 37 patients of the miglitol group (mainly flatulence and mild hypoglycaemia) and 2 of the placebo group. Urinary glucose was rendered negative in 41 patients in the miglitol group only. Thus miglitol appears to be a safe and effective adjunct in the management of Type 2 DM, in association with insulin.

1-Deoxynojirimycin↗
PubMed1998

Carnitine acetyltransferase is not a cytosolic enzyme in rat heart and therefore cannot function in the energy-linked regulation of cardiac fatty acid oxidation.

The subcellular location of cardiac carnitine acetyltransferase (CAT) was investigated by measuring the release of carnitine acetyltransferase and of marker enzymes from isolated rat myocytes permeabilized with digitonin. Additionally, the carnitine acetyltransferase activity exposed to the cytosolic compartment was quantified. The results indicate that soluble acetyl transferase is not present in the cytosol, and that only 5% of the cellular carnitine acetyltransferase activity is positioned to catalyse the formation of cytosolic acetyl coenzyme A. This situation makes it unlikely that the energy-linked regulation of cardiac fatty acid oxidation proceeds by mechanisms which require the conversion of acetylcarnitine to acetyl coenzyme A in the cytosol.

Animals↗
PubMed1998

Inability of galactoside-specific mistletoe lectin to inhibit N-methyl-N-nitrosourea-induced tumor development in the urinary bladder of rats and to mediate a local cellular immune response after long-term administration.

Extracts from mistletoe (Viscum album L.) are assumed to exert an antineoplastic activity through their toxicity at high doses or by immunomodulation by nanogram quantities of a lectin. They are used as an unconventional therapy modality in the management of a wide range of cancer diseases, although no anticancer potential has yet been demonstrated. This prompted us to study the effect of galactoside-specific lectin (VAA)--a major protein constituent of mistletoe with immunomodulatory properties--on chemically induced tumor development in the urinary bladder of rats and on the local cellular immune response after long-term administration. To induce urothelial neoplasms N-methyl-N-nitrosourea (MNU) was administered in a single intravesical dose (7.5 mg/kg body weight). Highly purified VAA was given subcutaneously at its immunomodulatory dose (1 ng/kg body weight) twice a week over the total experimental period of 15 months. The incidences of epithelial bladder tumors were 25.0% following administration of MNU alone and 22.9% in the rats additionally receiving VAA, which proved not to be significantly different (P = 0.81). Quantitative immunohistochemistry analyzing a panel of immune cell types, including T lymphocytes, T helper/inducer cells (CD4), T suppressor/cytotoxic cells (CD8), T cells positive for interleukin-2 receptor (CD25), B lymphocytes and plasma cells, macrophages, natural killer cells, granulocytes and all leukocytes expressing the leukocyte common antigen (CD45), yielded no evidence for the ability of VAA to stimulate a substantial cellular immunological reaction in the wall of the normal urinary bladder or during urothelial carcinogenesis. In conclusion, the current experimental findings provide no support at all that the galactoside-specific mistletoe lectin is capable of inhibiting chemically induced bladder carcinogenesis and triggering a local cellular immune response after prolonged application. It thus seems highly improbable that commercial mistletoe preparations or VAA will be effective in the management of human bladder cancer by a cell-mediated immunological mechanism.

Adjuvants, Immunologic↗
PubMed1998

Biochemical and genetic characterization of benzylsuccinate synthase from Thauera aromatica: a new glycyl radical enzyme catalysing the first step in anaerobic toluene metabolism.

Toluene is anoxically degraded to CO2 by the denitrifying bacterium Thauera aromatica. The initial reaction in this pathway is the addition of fumarate to the methyl group of toluene, yielding benzylsuccinate as the first intermediate. We purified the enzyme catalysing this reaction, benzylsuccinate synthase (EC 4.1.99-), and studied its properties. The enzyme was highly oxygen sensitive and contained a redox-active flavin cofactor, but no iron centres. The native molecular mass was 220 kDa; four subunits of 94 (alpha), 90 (alpha'), 12 (beta) and 10 kDa (gamma) were detected on sodium dodecyl sulphate (SDS) gels. The N-terminal sequences of the alpha- and alpha'-subunits were identical, suggesting a C-terminal degradation of half of the alpha-subunits to give the alpha'-subunit. The composition of native enzyme therefore appears to be alpha2beta2gamma2. A 5 kb segment of DNA containing the genes for the three subunits of benzylsuccinate synthase was cloned and sequenced. The masses of the predicted gene products correlated exactly with those of the subunits, as determined by electrospray mass spectrometry. Analysis of the derived amino acid sequences revealed that the large subunit of the enzyme shares homology to glycyl radical enzymes, particularly near the predicted radical site. The highest similarity was observed with pyruvate formate lyases and related proteins. The radical-containing subunit of benzylsuccinate synthase is oxygenolytically cleaved at the site of the glycyl radical, producing the alpha'-subunit. The predicted cleavage site was verified using electrospray mass spectrometry. In addition, a gene coding for an activating protein catalysing glycyl radical formation was found. The four genes for benzylsuccinate synthase and the activating enzyme are organized as a single operon; their transcription is induced by toluene. Synthesis of the predicted gene products was achieved in Escherichia coli in a T7-promotor/polymerase system.

Amino Acid Sequence↗
PubMed1998

Endurance training in females: changes in beta-endorphin and ACTH.

Previous results from endurance training in women have been discrepant in regard to influences on basal and maximum adrenocorticotropin (ACTH) and beta-endorphin (beta-EP) concentrations before and after exhaustive exercise. A group of 23 untrained young women ran 3 times a week for 30 min at an individual specific intensity corresponding to their respective anaerobic threshold, derived from the lactate performance curve obtained from prior treadmill testing. ACTH and beta-EP were measured at rest, as well as 5 and 30 min after exhaustive progressive spiroergometric treadmill running, both before and after the 8 week endurance training program. Basal beta-EP did not change after training, but less elevated concentrations were measured both 5 (p < 0.05) and 30 min (p < 0.05) after exercise, after the training program. In contrast, the resting concentration of ACTH increased significantly; the respective maximum concentration was less elevated after 5 min and much less elevated 30 min after the exercise (p < 0.05). Positive correlations were found after the exhaustive exercise between beta-EP and ACTH, as well as between maximum lactate and ACTH. Training was associated with significant changes in maximum running speed (p < 0.01), maximum oxygen uptake (p < 0.01) and the running speed at the anaerobic threshold (p < 0.05). Maximum lactate and the level of perceived exertion remained unchanged, showing a similar level of exhaustion. Our results indicate that endurance training modulates the hormonal responses of beta-EP and ACTH to comparable workloads of high intensity. After the training program the maximum concentrations are significantly lower during the recovery period. The tendency to elevated basal ACTH, and thus elevated cortisol, might be a new factor to consider in evaluation of endurance training induced hormonal disturbances in women.

Adrenocorticotropic Hormone↗
PubMed1998

Replication analysis of a putative susceptibility locus (EGI) for idiopathic generalized epilepsy on chromosome 8q24.

PURPOSE: The present replication study was designed to test the validity of a previously mapped susceptibility locus (EGI) for common subtypes of idiopathic generalized epilepsy (IGE) in chromosomal region 8q24. METHODS: Thirty-eight multiplex families of probands with common IGE syndromes were included in the present study. Parametric and nonparametric multipoint linkage analyses were conducted between the IGE trait (either "idiopathic" generalized seizure or generalized spike-wave EEG discharges) and three microsatellite polymorphisms (D8S256, D8S284, D8S1128) encompassing the putative EGI locus. RESULTS: Parametric and nonparametric multipoint linkage analysis provided no evidence for linkage between the IGE trait and the markers encompassing the putative EGI locus. Moreover, we noted no indication favoring linkage to this chromosomal region in two distinct subsets of families subdivided by the absence (n = 18) or presence (n = 20) of family members with juvenile myoclonic epilepsy (JME). CONCLUSIONS: We failed to replicate evidence of a major locus (EGI) for common familial IGE in chromosome region 8q24. On the contrary, our present parametric linkage results provide evidence against linkage across the region under a broad range of genetic models. If there is a susceptibility locus for IGE in this region, the effect size or the proportion of linked families is too small to detect linkage in these families. Taking into account the problems in replicating initial linkage claims in oligogenic traits, further linkage studies in additional family sets are necessary to evaluate the validity of the previous linkage finding.

Chromosome Mapping↗
PubMed1997

[Perforation of the esophagus after esophageal manometry].

HISTORY AND FINDINGS: A 75-year-old man was admitted for oesophageal manometry because of dysphagia for the past 2 years and retrosternal burning sensation unrelated to exercise. His general condition was appropriate for his age. INVESTIGATIONS: An oesophagogram showed corkscrew-like deformation of a diffuse oesophageal spasm. The first, but incomplete, manometry recorded clearly propulsive contractions with markedly raised and prolonged pressure, as in "nutcracker oesophagus". The lower oesophageal sphincter could not be demonstrated initially. Subsequent pH measurements provided no evidence for increased gastrooesophageal reflux. TREATMENT AND FURTHER COURSE: After the first manometry conservative treatment was initiated with molsidomine, nifedipine and nitrospray sublingual, but the dysphagia was not significantly improved. A second manometry was performed before a planned surgical exploration. Placing of the catheter was again difficult and mild resistance experienced. Endoscopy revealed only minimal, presumably superficial, mucosal lesions. 2 days later bilateral pleural effusions together with mediastinitis occurred. Conservative treatment was continued until finally a distal oesophageal perforation was demonstrated. At surgery the perforation was seen and a oesophagectomy with gastric pull-through and intrathoracic anastomosis performed. However, the patient died of septic multi-organ failure. CONCLUSIONS: Oesophageal manometry is a safe but invasive method with few complications for measuring oesophageal motility. Although this has not previously been reported, oesophageal perforation with mediastinitis may end fatally, if the particular circumstances are unfavourable. In addition to special anatomical features, type and state of the manometric catheter may present a risk factor.

Aged↗
PubMed1997

Cloning and expression of the fadH gene and characterization of the gene product 2,4-dienoyl coenzyme A reductase from Escherichia coli.

The fadH gene coding for an NADPH-dependent 2.4-dienoyl-CoA reductase from Escherichia coli has been cloned by the polymerase chain reaction. This gene is located at 67.65 min on the E. coli chromosome. The complete open reading frame contains 2019 bp coding for the processed protein of 671 amino acid residues, with a calculated molecular mass of 72.55 kDa, which lacks the N-terminal methionine. Construction and expression of the plasmid pNDH, which contained the fadH gene under the control of the T7 promoter, resulted in a 110-fold increase in the reductase activity above the level detected in E. coli cells containing the control vector. The kinetic parameters of the purified reductase were determined to be 50 microM and 2.3 microM for the Km values of NADPH and 2-trans, 4-trans-decadienoyl-CoA, respectively, and 16 s(-1) for the k(cat) value. Analysis of the kinetic data revealed that the reaction catalyzed by this enzyme proceeds via a ping-pong mechanism. The observed dissimilarity between the E. coli and mammalian 2,4-dienoyl-CoA reductase sequences suggests that they have evolved from distinct ancestral genes. Sequence analysis also suggests that the N-terminal part of the E. coli reductase contains the FAD-binding domain whereas the NADPH-binding domain is located in the C-terminal region of the protein.

Amino Acid Sequence↗
PubMed1997

Detection of impaired intrapulmonary convective mixing by aerosol bolus dispersion in patients with emphysema.

The broadening of an inhaled aerosol bolus (aerosol bolus dispersion) during respiration provides a noninvasive, nonradioactive, and easy to perform technique which is a measure of the extent of convective gas mixing processes in the lung and symmetry of ventilation during the breathing cycle. In this study, this technique was evaluated for the ability to detect ventilation inhomogeneities in pulmonary emphysema (PE). An aerosol bolus undergoes changes in shape between its inspiration and expiration. In comparison with the inhaled bolus, the exhaled bolus is more spread because of convective mixing and may have a shift in the location of the mode caused by asymmetries of filling and emptying of lung units. We hypothesized that in PE these changes differ from healthy subjects and are related to lung health. Twenty nine patients with PE inhaled 25 ml boluses containing 0.9 micron monodisperse aerosol particles into volumetric lung depths of 200, 400, 600, and 800 cm3. The control group were 79 healthy subjects. As each bolus was expired, we measured bolus dispersion (volumetric width at one-half aerosol concentration peak height) and mode shift. In patients with PE exhaled boluses were significantly broader than those exhaled by normal subjects at all volumetric lung depths. At a lung depth of 800 cm3, patients showed a bolus dispersion that was 52% greater than that of healthy subjects (p < 0.0001) and they exhaled the bolus mode earlier (p < 0.0001). Aerosol bolus parameters were not influenced by anthropometric data. Pulmonary function parameters indicating obstruction showed a weak negative correlation with aerosol bolus parameters (R2 < 0.4). The bolus parameters appeared to be supplemental to conventional lung function tests and significantly indicated marked ventilation asymmetry and altered convective gas transport in pulmonary emphysema. The results support the use of the aerosol bolus dispersion test in assessing peripheral parenchymal lung injury.

Administration, Inhalation↗
PubMed1997

[Epiluminescence microscopic characteristics of small malignant melanoma].

17% of malignant melanomas (n = 100) investigated in a dermatologic practice were less than 6 mm in maximal diameter (median diameter: 4.0 +/- 0.9 mm). The median age of the 17 patients at diagnosis of small-diameter melanomas was 42 years. The essential epiluminescence microscopic and histopathologic features of these small melanomas resembled those of larger lesions, although their clinical criteria differed from the classic ABCDs.6 (35.3%) of the small melanomas were were found to be in situ. This percentage was nearly similar to those in situ lesions within the group of melanomas of 6 mm in diameter or larger (38.3%). The remaining 11 small lesions were classified as invasive from Clark's level I to V, including all classic histogenetic types (superficial spreading, nodular, unclassified, desmoplastic). The median thickness of the small invasive melanomas was 0.76 +/- 0.23 mm. 7 small melanomas had apparent histologic remnants of a melanocytic nevus. Epiluminescence microscopic features of the melanomas were evaluated and statistically compared with those of 100 dysplastic nevi and 50 spindle cell nevi. The technique of epiluminescence microscopy allowed the identification of such malignant melanomas that could not be discerned by the naked eye or by a pocket-lens.

Chi-Square Distribution↗
PubMed1997

Lack of an antitumoral effect of immunomodulatory galactoside-specific mistletoe lectin on N-methyl-N-nitrosourea-induced urinary bladder carcinogenesis in rats.

The aim of the present animal experiment was to study the effect of galactoside-specific lectin or agglutinin (VAA) from mistletoe (Viscum album L.) on chemically induced tumor development in the urinary bladder of rats. Since VAA has been shown to exert a remarkable immunomodulating effect, any change in tumor formation would indicate a lectin-triggered immune control of urothelial carcinogenesis in the used model. To produce vesical neoplasms the direct-acting urothelial carcinogen N-methyl-N-nitrosourea (MNU) was administered at a single intravesical dose (7.5 mg/kg body weight). Highly purified VAA was given subcutaneously twice a week at the immunomodulatory dose of 1 ng/kg body weight over a period of 6 months during the critical phases of tumor development. After a total experimental time of 15 months the incidence of epithelial bladder tumors was 29.3% in controls versus 27.9% in rats additionally receiving the lectin and thus not significantly different in both experimental groups. There were, moreover, no substantial differences in the histopathologic spectrum of epithelial tumors induced, their patterns of growth, grades of cellular malignancy and local extension. The frequency and histopathology of mesenchymal bladder tumors as well as the incidence and morphology of carcinomas of the ureters and renal pelves also proved to be similar in controls and in rats treated with VAA. In conclusion, the present data provide no evidence for a modifying or even inhibitory effect of the immunomodulatory galactoside-specific mistletoe lectin on experimental urothelial carcinogenesis.

Adjuvants, Immunologic↗
PubMed1997

Regression of gastric MALT lymphoma after eradication of Helicobacter pylori is predicted by endosonographic staging. MALT Lymphoma Study Group.

BACKGROUND & AIMS: Recent studies suggest that eradication of Helicobacter pylori may result in complete regression of low-grade lymphoma of the gastric mucosa-associated lymphoid tissue (MALT). Which patients benefit from this treatment is unknown. The aim of this study was to prospectively study whether staging by echoendoscopy predicts the outcome of treatment of MALT lymphoma by eradication of H. pylori. METHODS: Twenty-two patients positive for H. pylori with low-grade gastric B-cell MALT lymphoma were examined by echoendoscopy at the time of diagnosis. Treatment for H. pylori consisted of a 2-week course of oral omeprazole and amoxicillin. Patients were followed up by endoscopy and biopsy. RESULTS: H. pylori was eradicated in all patients. Complete regression of MALT lymphoma was observed in 12 patients (54%), partial regression in 5 patients (23%), and no response in 5 patients (23%) during follow-up. Twelve of 14 patients with lymphoma restricted to the mucosa or submucosa (stage E-I1) at echoendoscopy, but none of the 10 patients with higher stage (P < 0.01), showed complete regression of MALT lymphoma. In stage E-I1 patients, the probability of complete regression of lymphoma was 60% at 6, 79% at 12, and reached 100% at 14 months, respectively. CONCLUSIONS: Staging of gastric low-grade MALT lymphomas by endoscopic ultrasonography allows prediction of the response to therapy by eradication of H. pylori.

Adult↗
PubMed1997

The validity of the telemetric system CORTEX X1 in the ventilatory and gas exchange measurement during exercise.

With the portable spirograph CORTEX X1 both the oxygen consumption and the carbon dioxide output can be determined. Therefore, the aim of the present study was to determine the accuracy of the CORTEX X1 in measuring F(E)O2, F(E)CO2 and V(E) when attached to a motor-driven mechanical syringe and to validate the CORTEX X1 against a standardized breath-by-breath system during a graded bicycle ergometry. Fifteen subjects (8 male, 7 female; 26.7+/-3.3 years) performed two graded exercise tests on a bicycle ergometer (50 W incline every 3 min) until volitional fatigue in randomized order. During rest and during the last 30 s of each step ventilatory and gas exchange parameters were measured with the CORTEX X1 and the OXYCONgamma. At rest and at each step no significant differences exist for VO2 (F = 0.97) and VCO2 (F = 0.90). The orthogonal regression equation of the VO2-values was VO2(X1) = -75.5 + 1.01 x VO2(Oxy) and the equation of the VCO2-values was VCO2(X1) = 21.7-1.008 x VCO2(Oxy). The VO2-max-values were nearly the same: 3569+/-924 ml/min (Oxy) and 3497+/-993ml/min (X1). Similar findings were made with regard to VCO2max 4117+/-1010 ml/min (Oxy) and 4126+/-1090 ml/ min. (X1). Maximal values for heart rate were 181+/-10 beats/ min (X1) and 180+/-8 beats/min (Oxy) (F=0.21), for maximal power 256+/-64 W (X1) and 257+/-63 (Oxy) (F = 0.0001) and for maximal ventilation 118+/-31 l/min) and 120+/-35 l/min (Oxy) (F = 0.03) with no significant difference. When attached to the motor-driven syringe V(E) was accurately measured up to 288 l/ min. Over a period of 40 min there was no drift observed in F(E)O2 and F(E)CO2. In conclusion, with the CORTEX X1 VO2 and VCO2 can be accurately determined.

Adult↗
PubMed1997

Behavioural and functional neurotoxicological changes caused by cadmium in a three-generational study in rats.

1. Three consecutive generations of Wistar rats were orally treated by gavage with 3.5, 7.0 or 14.0 mg/kg cadmium (in form of cadmium chloride diluted in distilled water) over the period of pregnancy, lactation and 8 weeks after weaning. 2. Behavioural (open field behaviour) and electrophysiological (spontaneous and evoked cortical activity, etc.) parameters of male rats from each generation were investigated at the age of 12 weeks. 3. The main behavioural outcomes were change in vertical exploration activity (rearing) and increased exploration of an open field centre. The spontaneous and evoked electrophysiological variables showed dose- and generation-dependent changes (increased frequencies in the electrocorticogram, lengthened latency and duration of evoked potentials, etc.) signalling a change in neural functions. 4. The data show that low-level, multigeneration exposure to inorganic cadmium can affect functions of the nervous system. This suggests that cadmium exposed human populations may be at risk of developing nervous system disorders.

Animals↗