Probabilistic reinforcement and neurotic breakdown in unrestrained dogs]

The substitution of a constant reinforcement for a random one with a probability of 0.5 in experiments on two dogs with a simple motor stereotype was attended with nervous breakdowns with motor excitation, inadequate orienting reactions or passive-defensive behaviour. The change in the probability of reinforcement from 0.5 to 0.3 had a positive effect in experiments on one dog, while in the other it developed drowsiness. In two other dogs with a complicated stereotype, the change in the mode of reinforcement was attended with a peculiar preventive effect of probabilistic, but ordered reinforcement in experimental surroundings, including signals with a probabilistic random reinforcement as well. In this case the dogs displayed primarily signs of emotional stress only. Behaviour was somewhat disturbed in one animal only when testing signals with a probabilistic random reinforcement.     

Influence of prior and visual information on eye movements in amblyopic children

This study analyzed the characteristics of pursuit and assessed the influence of prior and visual information on eye velocity and saccades in amblyopic and control children, in comparison to adults. Eye movements of 41 children (21 amblyopes and 20 controls) were compared to eye movements of 55 adults (18 amblyopes and 37 controls). Participants were asked to pursue a target moving at a constant velocity. The target was either a ‘standard’ target, with a uniform color intensity, or a ‘noisy’ target, with blurry edges, to mimic the blurriness of an amblyopic eye. Analysis of pursuit patterns showed that the onset was delayed, and the gain was decreased in control children with a noisy target in comparison to amblyopic or control children with a standard target. Furthermore, a significant effect of prior and visual information on pursuit velocity and saccades was found across all participants. Moreover, the modulation of the effect of visual information on the pursuit velocity by group, that is amblyopes or controls with a standard target, and controls with a noisy target, was more limited in children. In other words, the effect of visual information was higher in control adults with a standard target compared to control children with the same target. However, in the case of a blurry target, either in control participants with a noisy target or in amblyopic participants with a standard target, the effect of visual information was larger in children.

     

Measles immunisation in children with allergy to egg.

OBJECTIVE--To examine the occurrence of adverse reactions to measles vaccine given as a single dose to children with egg allergy, and to determine if the administration of single dose to children with a positive result in an intradermal skin prick test with the vaccine is associated with adverse reactions. DESIGN--Review of results of immunisation and prospective study of 96 consecutively presenting children given intradermal skin testing with the vaccine. SETTING--Children''s allergy centre. SUBJECTS--410 children sensitive to egg referred to the allergy unit for advice about measles immunisation. MAIN OUTCOME MEASURES--Nature and severity of reactions associated with the administration of measles vaccine. RESULTS--All children had a positive result in a skin prick test with egg white, and five had a positive result in a skin prick test with vaccine. Of 96 consecutive children, 46 had a positive result in an intradermal test with vaccine. After immunisation with a full dose (0.5 ml) of vaccine adverse reactions were associated with a mild reaction in four children, none of whom required treatment. Only one of the 46 children with a positive result in an intradermal vaccine skin test had a reaction associated with vaccine administration. None of the children with a positive result in a skin prick test with measles vaccine reacted to the vaccine. The rate of minor reactions to the vaccine not requiring treatment was 0.98% (95% confidence interval 0.27% to 2.48%) and serious reactions requiring treatment was 0% (0% to 0.9%). CONCLUSION--Children with IgE mediated allergic reactions to egg protein should be investigated and managed by practitioners with special knowledge in this subject. Measles immunisation should be performed in a setting where any adverse reactions can be dealt with appropriately. Skin tests and measles vaccine and desensitisation are not necessary.     

Excitation of waves in an inhomogeneous plasma

The evolution of initial perturbations in a spatially inhomogeneous cold electron plasma in the absence of an external magnetic field is considered. The excitation of both continuous-spectrum bulk plasma waves and surface plasma waves with a discrete frequency spectrum is investigated. Analytic solutions are obtained in the long-wavelength limit, and the excitation of waves of arbitrary length is analyzed numerically. The local, integral, and spatial spectra are calculated, as well as the field structures and dispersion properties of waves in waveguides filled nonuniformly with a plasma. It is shown that, in a plasma with a smooth boundary, there also exist surface waves with a discrete spectrum (although with somewhat different properties as compared to those in a plasma with a sharp boundary), which are excited together with continuous-spectrum bulk waves during the evolution of the initial perturbation.     

Dynamics of Scroll Wave in a Three-Dimensional System with Changing Gradient

The dynamics of a scroll wave in an excitable medium with gradient excitability is studied in detail. Three parameter regimes can be distinguished by the degree of gradient. For a small gradient, the system reaches a simple rotating synchronization. In this regime, the rigid rotating velocity of spiral waves is maximal in the layers with the highest filament twist. As the excitability gradient increases, the scroll wave evolutes into a meandering synchronous state. This transition is accompanied by a variation in twisting rate. Filament twisting may prevent the breakup of spiral waves in the bottom layers with a low excitability with which a spiral breaks in a 2D medium. When the gradient is large enough, the twisted filament breaks up, which results in a semi-turbulent state where the lower part is turbulent while the upper part contains a scroll wave with a low twisting filament.     

Somatostatin release in the hippocampus in the kindling model of epilepsy: a microdialysis study

Somatostatin biosynthesis in the hippocampus is activated during and following kindling epileptogenesis. The aim of this study was to investigate whether this phenomenon is associated with enhanced somatostatin release in vivo. Experiments have been run in awake, freely moving rats, implanted with a bipolar electrode in the right amygdala (for kindling stimulation), and with a recording electrode and a microdialysis probe in the left hippocampus. Basal somatostatin-like immunoreactivity (-LI) release was significantly greater in kindled than naive rats. In naive rats, a 2-min perfusion with 100 mM K(+) did not affect behavior and EEG recordings and nonsignificantly increased somatostatin-LI release; a 10-min K(+) perfusion evoked numerous wet dog shakes, electrical seizures (class 0; latency congruent with 8 min, duration congruent with 8 min), and somatostatin-LI release ( congruent with 350% of basal); and a single kindling after-discharge (4 +/- 3-s duration in the hippocampus) also evoked somatostatin-LI release ( congruent with 200% of basal). In kindled rats, a 2-min 100 mM K(+) perfusion evoked hippocampal discharges in three of seven animals (latency congruent with 2 min, mean duration congruent with 1.5 min) and increased somatostatin-LI release ( congruent with 250% of basal); a 10-min K(+) perfusion evoked behavioral seizures (class 1 to 5, latency congruent with 4 min, mean duration congruent with 12 min) with numerous wet dog shakes and robust somatostatin-LI release ( congruent with 350% of basal); and a kindling stimulation evoked generalized seizures (class 4 or 5, 77 +/- 15-s duration in the hippocampus) with remarkable somatostatin-LI release ( congruent with 300% of basal). These data demonstrate that hippocampal somatostatin release is increased in the kindling model in vivo.     

Is glycine a surrogate for a d‐amino acid in the collagen triple helix?

Collagen is the most abundant protein in animals. Every third residue in a collagen strand is a glycine with phi, psi = -70 degrees, 175 degrees. A recent computational study suggested that replacing these glycine residues with D-alanine or D-serine would stabilize the collagen triple helix. This hypothesis is of substantial importance, as the glycine residues in collagen constitute nearly 10% of the amino acid residues in humans. To test this hypothesis, we synthesized a series of collagen mimic peptides that contain one or more D-alanine or D-serine residues replacing the canonical glycine residues. Circular dichroism spectroscopy and thermal denaturation experiments indicated clearly that the substitution of glycine with D-alanine or D-serine greatly disfavors the formation of a triple helix. Host-guest studies also revealed that replacing a single glycine residue with D-alanine is more destabilizing than is its replacement with L-alanine, a substitution that results from a common mutation in patients with collagen-related diseases. These data indicate that the glycine residues in collagen are not a surrogate for a D-amino acid and support the notion that the main-chain torsion angles of a glycine residue in the native structure (especially, phi > 0 degrees ) are critical determinants for its beneficial substitution with a D-amino acid in a protein.     

Analysis of the molecular interaction of the farnesyl moiety of transducin through the use of a photoreactive farnesyl analogue

Farnesylation of the gamma-subunit of the retinal G-protein, transducin (Talpha/Tbetagamma), is indispensable for light-initiated signaling in photoreceptor cells. However, the farnesyl-mediated molecular interactions important for signaling are not well understood. To explore this issue, we created a functional Tbetagamma analogue in which the farnesyl group was replaced with a (3-azidophenoxy)geranyl (POG) group, a novel farnesyl analogue with a distal photoreactive azido group. In the presence of lipid membranes and/or Talpha-GDP, UV irradiation of POG-modified Tbetagamma (POG-Tbetagamma) invariably yielded a cross-linked product Tgamma-Tbeta, reflecting a constitutive interaction of the Tgamma C-terminal lipid with Tbeta. In addition to the Tgamma-Tbeta adduct, a Tgamma-Talpha cross-link was detected in the aqueous fraction. Reconstitution of POG-Tbetagamma with Talpha and light-activated rhodopsin (Rh) in photoreceptor membranes resulted in cross-linking of Tgamma with a glycerophospholipid, indicating molecular interaction of the farnesyl group with cellular membranes. The Tgamma-phospholipid cross-link was observed only in the presence of both Talpha-GDP and Rh, and was abolished by the addition of GTPgammaS or by replacing Rh with opsin. These findings suggest a transient farnesyl-membrane interaction occurs only in a signaling state formed in a transducin-Rh ternary complex. On the other hand, UV irradiation of POG-Tbetagamma in a soluble complex with phosducin, a negative regulator of G-protein, yielded a Tgamma-phosducin adduct in addition to the Tgamma-Tbeta cross-link. These results illustrate that, rather than being a static membrane anchor, the farnesyl moiety plays an active role in the dynamics of protein-protein and protein-membrane interactions at defined steps in the signal transduction process.     

Effects of Feeding a Histidine-excess Diet and Subsequent Starvation on Liver and Muscle Glycogen,and on Serum Glucose

The effects of feeding with a histidine-excess diet and subsequent starvation on liver and muscle glycogen, and on serum glucose were investigated in young and adult rats.

Feeding with a histidine-excess diet resulted in the accumulation of liver glycogen in both young and adult rats. The hepatic glycogen continued to decrease during starvation, and the liver became almost totally depleted of glycogen after starvation for 48 hr. Glycogen in the liver of young rats starved for 24 hr after previous feeding with a histidine-excess diet was significantly higher than that of young rats starved for 24 hr after previous feeding with a basal diet.

Muscle glycogen after feeding and subsequent starvation was not affected by the types of diets fed previously, muscle glycogen during starvation showing a slight decrease in young rats and a slight increase in adult rats.

Feeding with a histidine-excess diet caused a significant decrease of serum glucose in young rats, but not in adult rats. Serum glucose in young rats was markedly reduced by starvation after previous feeding with a basal diet, but not after previous feeding with a histidine-excess diet. In adult rats, there were no changes in serum glucose between rats starved after feeding with either a basal diet or a histidine-excess diet, and serum glucose was decreased slightly by starvation after feeding with the test diets.

The overall results indicate that the maintenance of serum glucose in young rate even during starvation after previous feeding with a histidine-excess diet might be partially concerned with the export of glucose from the accumulated glycogen in the liver due to the diet.     

X-ray-induced mutation spectra of different germ-cell stages of Drosophila males with a double marked Y-chromosome and either a normal X-or a ring-X-chromosome (author's transl)

Different germ-cell stages of Drosophila males with a double marked Y-chromosome and either a normal X- or a ring-X chromosome were irradiated with X-rays, inducing the following aberrations: chromosome loss, chromosome gain (XYX-females), partial Y loss and isochromosomes of the Y-chromosome.Doses of 520 rad in spermatocytes and spermatids and 2600 rad in sperm, produced the same effect in these stages with regard to the chromosome loss in the males with a normal X, and the following results were obtained: (a) The partial Y loss in postmeiotic stages is small in comparison with spermatocytes in both stocks. This could mean that in spermatocytes this aberration is determined by exchange processes which can only be induced and/or detected in premeiotic stages. (b) In spermatocytes and mature sperm of males with a ring-X chromosome, the chromosome loss was 2.9 times greater than in those with a normal X. In spermatids of the males with a ring-X the rate of loss was only 1.5 times greater. In spermatocytes of either males with a ring-X or a normal X a similar high rate of isochromosomes could be induced. However, in spermatids and mature sperm the rate of induction of isochromosomes was found to be very small. These results seem to indicate that in mature sperm the rejoining of breaks in the Y-chromosome takes place before, and in the X-chromosome usually after the replication. If in post-meiotic stages of Drosophila the X- and Y-chromosomes existed as chromatid-like subunits then in spermatids these should behave as a structural unit.In sperm we were able to induce similar frequencies of individuals with a single isochromosome type in all body cells as of individuals with two types of isochromosomes (isochromosome mosaics). This result seems to indicate that after irradiation of sperm one of the first two division nuclei is lethal in an proportion of the zygotes.     

Studies on the control of antibody synthesis. XVI. Effect of immunodepression on antibody affinity

The relationship between depression in the magnitude of the immune response and a decrease in affinity of the antibody produced was examined in three different models of immuno-depression (B-cell clonal deletion tolerance, specific suppressor T-cell activity, and anti-genie competition). In B-cell clonal deletion tolerance and in antigen-specific, suppressor T-cell-mediated immunodepression, a small decrease in magnitude (50% or less) is associated with a marked decrease in high-affinity, plaque-forming cells. In contrast, with nonspecific immunodepression, due to antigenic competition, a depression in affinity is only seen when there is a marked (85%) reduction in the magnitude of the response. The results are consistent with the view that when the mechanism of immunodepression involves interaction of antigen with antigen-specific B cells there is a disproportionate loss of high-affinity, antibody-producing cells relative to the decrease in magnitude. In contrast, with nonspecific immuno-depression, where the decrease in affinity is presumably due to inefficient expansion of high-affinity clones, an effect on affinity is only observed in association with a marked depression in the magnitude of the response.     

Pulse oximetry at the roadside: a study of pulse oximetry in immediate care.

The measurement of tissue oxygen saturation with a pulse oximeter is of proved value in the hospital setting. The development of a portable oximeter has allowed this investigation to be performed during the prehospital phase of a patient''s care. Pulse oximetry was performed at the roadside in 25 patients with abnormal trauma scores and found to be of benefit in detecting and monitoring hypoxia in patients with airway obstruction, depressed respiration due to head injury, and, in particular, with closed chest injuries. There were no practical difficulties associated with the use of the instrument either at the roadside or in a moving ambulance. The portable pulse oximeter is a valuable aid in the prehospital monitoring of patients with trauma.     

Tumor growth inhibition by sonodynamic therapy using a novel sonosensitizer

Sonodynamic therapy (SDT) with low-intensity ultrasound combined with a sonosensitizer may be a promising approach to cancer therapy. Use of ultrasound has the advantage of being noninvasive, with deep-penetration properties, and convenient because of the low or no sensitivity of sonosensitizers to light. In this study, SDT with a novel sonosensitizer (a porphyrin derivative) was evaluated in vitro and in vivo. Ultrasound irradiation with a sonosensitizer elicited potent sonotoxicity in vitro without the danger of phototoxicity. The sonotoxic effect was mediated by reactive oxygen species (ROS) and was reduced by ROS scavengers. Cell membrane lipid peroxidation increased significantly just after ultrasound irradiation with a sonosensitizer, but there was no increase in apoptosis. In an in vivo mouse xenograft model, SDT with a sonosensitizer markedly inhibited tumor cell growth. The skin hypersensitivity after light exposure was not observed in a sonosensitizer-treatment group, consistent with the in vitro findings. These results suggest that ROS generated by SDT with a sensitizer can damage tumor cells, resulting in necrosis and prevention of tumor growth. This noninvasive treatment with no adverse effects such as skin sensitivity is therefore promising for therapy of cancers located deep within patients.     

基于小波分析的大豆叶绿素a含量高光谱反演模型

 2003和2004年分别在长春市良种场和中国科学院海伦黑土生态实验站实测了大田耕作与水肥耦合作用下大豆（Glycine max）冠层高光谱反射率 与叶绿素a含量数据,对光谱反射率、微分光谱与叶绿素a含量进行了相关分析;采用归一化植被指数(Normalized diffe rence vegetation index, NDVI)、土壤调和植被指数(Soil-adjusted vegetation index, SAVI)、再归一植被指数(Renormalized difference vegetation index, RDVI)、第二修正比值植被指数(Modified second ratio index, MSRI)等建立了大豆叶绿素a反演模型;应用小波分析对采集的光谱反 射率数据进行了能量系数提取,并以小波能量系数作为自变量进行了单变量与多变量回归分析,对大豆叶绿素a进行了估算。研究结果表明,大 豆叶绿素a 与可见光光谱反射率相关性较好,并在红光波段取得最大值(R²>0.70),但在红边处,微分光谱与大豆叶绿素a的相关性较反射率好 得多,在其它波段则相反;由NDVI、SAVI、RDVI、MSRI等植被指数建立的估算模型可以提高大豆叶绿素a的估算精度（R²>0.75）;小波能量系 数回归模型可以进一步提高大豆叶绿素a含量的估算水平,以一个特定小波能量系数作为自变量的回归模型,大豆叶绿素a回归决定系数R²高达 0.78;多变量回归分析结果表明,大豆叶绿素a实测值与预测值的线性回归决定系数R²均高达0.85。以上结果表明, 小波分析可以对高光谱进 行特征变量提取,并可在一定程度上提高大豆生理参数反演精度。     

Negatively charged phospholipids and their position in the cholesterol affinity sequence

The effects of low concentrations of cholesterol in mixtures of a negatively charged phospholipid (phosphatidylserine or phosphatidylglycerol) and another phospholipid (phosphatidylcholine, sphingomyelin or phosphatidylethanolamine) have been studied by differential scanning calorimetry. Only mixtures which showed a gel phase miscibility gap have been employed. It was demonstrated that in mixtures with phosphatidylethanolamine, cholesterol was preferentially associated with the negatively charged phospholipid, regardless whether this species represented the component with the high or with the low transition temperature in the mixture. In mixtures of a negatively charged phospholipid and phosphatidylcholine, cholesterol associated with the negatively charged phospholipid; when the phosphatidylcholine was the species with the low transition temperature, cholesterol had an affinity for the phosphatidylcholine and for the negatively charged phospholipid as well. Cholesterol, in a mixture of sphingomyelin with a high and phosphatidylserine with a low transition temperature, was preferentially associated with sphingomyelin.From these experiments it is concluded that phospholipids show a decrease in affinity for cholesterol in the following order: sphingomyelin ? phosphatidylserine, phosphatidylglycerol > phosphatidylcholine ? phosphatidylethanolamine.     

Schistosoma mansoni: immunoblot analysis of adult worm proteins

Proteins of adult Schistosoma mansoni were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and assayed in immunoblots for reactions with individual mouse sera. Four weeks after a heavy infection with a few hundred cercariae, IgG antibodies directed predominantly against a protein of 31 kDa were detected. The protein was only weakly recognized by antibodies of mice harboring a 4-week-old light infection with about 60 cercariae. After 6 weeks or more, mice infected with either dose formed antibodies, not only against the 31-kDa protein and a 67-kDa protein, but also against a number of other components. While reactions with the 31- and 67-kDa proteins occurred with sera of all individual mice of four different strains, the reactions with other components were less consistently observed. Mice vaccinated with a heavy or light dose of 20,000-rad-irradiated cercariae did not form antibodies detectable in the blotting system. However, in immunofluorescence assays with living skin schistosomula, but not lung schistosomula, antibodies against the larval surface were detected with all sera obtained 4 weeks after infection or vaccination. In addition, immunofluorescence studies using the same sera and sectioned adult parasites demonstrated the presence of antibodies against the parasite surface in all sera except those obtained from mice exposed to a light infection with normal cercariae. Mice infected in this latter way were the only animals that did not develop a significant resistance against a challenge infection 4 weeks after exposure to normal or irradiated cercariae. The presence of an immunofluorescent reaction against the schistosome gut always coincided with a reaction of the sera with the 31-kDa protein in the immunoblots. Although a role in immune resistance could not be ascribed to any of the proteins reacting in the immunoblots, the data demonstrate important differences in the antibody specificities induced by various infection schemes.     

Twin pregnancy with complete hydatidiform mole and coexisting fetus following ovulation induction with a non-prescribed clomiphene citrate regimen: a case report

Introduction

Until now, studies on paracetamol given intravenously have mainly been performed with the pro-drug propacetamol or with paracetamol in preterm babies above 32 weeks of gestation. Studies in these babies indicate that intravenous paracetamol is tolerated well, however studies on the efficacy of intravenous paracetamol are lacking. There are no pharmacokinetic data on the administration of multiple doses of paracetamol in preterm babies with a gestational age below 32 weeks.

Case presentation

We present a case series of nine Caucasian preterm babies, six boys and three girls, with a mean gestational age of 28.6 weeks (range 25.9 to 31.6 weeks). Case one, a girl with a gestational age of 25 weeks and six days, presented with necrotizing enterocolitis. In the second case, a female baby with a gestational age of 26 weeks and two days presented with hematoma. In case three, a female baby with a gestation of 26 weeks and one day developed intraventricular hemorrhage. In case four, a male baby with a gestational age of 31 weeks and four days presented with pain after vacuum delivery. Case five, a female baby born after a gestation of 29 weeks and six days presented with hematoma. In case six, a male baby with a gestation of 30 weeks and six days presented with hematoma. In case seven, a male baby, born with a gestational age of 30 weeks and six days, presented with caput succedaneum and hematoma. In case eight, a male baby, born after a gestation of 28 weeks and four days, developed abdominal distention. Case nine, a female baby, born with a gestational age of 27 weeks and three days presented with hematoma. These babies were treated with intravenous paracetamol 15 mg/kg every six hours. Serum concentrations and aspartate transaminase were determined after prolonged administration. Pain scores were assessed using the Premature Infant Pain Profile.

Conclusion

Paracetamol serum concentrations ranged from 8 to 64 mg/L after eight to 12 doses of intravenous paracetamol. Adequate analgesia was obtained in seven babies. During paracetamol therapy the median serum level of aspartate transaminase was 20 U/L (range 12 to 186 U/L). This case series indicates that prolonged intravenous administration of paracetamol in preterm babies with a gestational age of less than 32 weeks is tolerated well in the first days after birth. However, in the absence of proper pharmacokinetic data in this age group we cannot advocate the use of paracetamol intravenously.     

Detection of protease activity in the wetted surface of gelatin-coated electrodes in air by AC impedance spectroscopy

As a step towards developing a biosensor which can detect airborne protease droplets, a biosensor which had previously been developed to detect protease in solution is shown to be capable of detecting different concentrations of protease in liquid films on the sensor surface in air. The biosensor measured impedance change due to proteolytic digestion of its gelatin coating. In saturated air there was a rise in impedance, with a loss in weight of the gelatin, in proportion to collagenase concentration. The addition of glycerol to the gelatin caused a lower impedance response and smaller loss in weight. A critical thickness of the gelatin layer prior to a more rapid change in the rate of impedance was noted, with and without the addition of glycerol. In low air humidity (40%), with gelatin, all collagenase concentrations produced a very similar rapid increase in impedance. However, with glycerol-enhanced gelatin, there was a clear distinction between the extent of impedance change with different collagenase concentrations. The application of these findings for use in the field of bioaerosol sampling is discussed.     

Toxicity of Trimethoprim-Sulphamethoxazole in Patients with Megaloblastic Haemopoiesis

Four consecutive patients with megaloblastic anaemia who also received therapy with trimethoprim-sulphamethoxazole all showed poor responses to specific haematinic therapy. This was attributed to trimethoprim, which suppressed reticulocyte responses in three cases and produced a pancytopenia in two and a falling haemoglobin with neutropenia in a third. A fourth patient, with pernicious anaemia, had a satisfactory reticulocyte response but experienced no clinical benefit until after withdrawal of trimethoprim.Trimethoprim seems not to be a safe form of therapy in patients with a megaloblastic process; many of the toxic reactions reported with this drug may be on the basis of an unrecognized megaloblastic form of haemopoiesis.     

Metabolic shift analysis at high cell densities

Abstract: In high cell density cultures it is virtually inevitable that the environment to which the cells are exposed is heterogeneous. Thus, with suspended cultures, individual cells are subject to temporal changes in their environment whereas with aggregated or immobilized cells, the culture can be considered as being formed by a number of subpopulations, each with its own environmental characteristics. In addition, in a high cell density environment, high concentrations of end products may negatively influence the growth rate. This may result in the selection of organisms with an altered metabolic behaviour or with a decreased sensitivity to the adverse effects of the product. We discuss the consequences of this heterogeneity with regard to carbon source metabolism in view of the ability of many bacterial species to adapt to environmental conditions. Selection of variant organisms was found to occur with Clostridium butyricum when grown for a prolonged time in a medium containing approx. I-50 mM glucose. In contrast to the original strain, these variants could sustain a high maximal growth rate in the presence of butyric acid. In addition, they had acquired the capacity to spontaneously form aggregates and were able to carry out a completely solventogenic fermentation. Heterogeneous metabolic activity in aggregated cells is demonstrated with cultures of Lactobacillus laevolacticus , an aggregateforming lactic acid bacterium that converts glucose completely to o-lactate. By using microelectrodes, we show that the fraction of metabolically active cells decreases with increasing aggregate size: in larger aggregates steep pH gradients occur with the effect that only the outer layer of the aggregate is metabolically active, i.e. contributes to lactic acid formation, whereas with smaller aggregates all cells remain active. As a result, the net specific lactic acid production rate of the population as a whole is not invariably increased with increased aggregate size.