Improved evaluation of back muscle SEMG characteristics by modelling.

Surface EMG (SEMG) as non-invasive method is a valuable tool in functional studies of movement co-ordination. The interpolation of the SEMG power (EMG mapping) gives information about intra- and inter-muscular co-ordination. It has been shown that SEMG maps of low back pain patients and healthy subjects differ. The only major drawback to SEMG is that volume conduction of muscle tissue, fat, and skin decreases the spatial and temporal resolution of signals. To improve the interpretation of SEMG signals, we have applied high pass filtering of cross covariance functions, which has proved to be useful in increasing the spatial resolution, to SEMG data of the back region. Experimental data demonstrate that SEMG signals from the back extensors show only rarely signs of action potential propagation. This behaviour, also described in the literature, can be explained by a model assuming short, deep muscle fibres, having bipolar end effects, with overlapping positions parallel to the fibre direction. This condition is fulfilled by the mm. multifidii et rotatores which are part of the m. erector spinae. Although the model is simplistic, the agreement between simulations and experiments is good.

Is there a close relationship between changes in amplitudes of distortion product otoacoustic emissions and hair cell damage after exposure to realistic industrial noise in guinea pigs?

In long-term experiments in awake guinea pigs (n = 12), distortion product otoacoustic emissions (DPOAEs) at various frequencies were measured repeatedly over 6-8 months. About 9 weeks after the first measurement, the animals were exposed to industrial noise (car industry, maximal intensity about 110 dB SPL) for 2 h. The amplitudes of DPOAE were measured prior to noise exposure and 10 min, 70 min, 1 day and 2 days after the noise exposure and then once every week. Three to four months after noise exposure, the animals were killed, and the cochleae were prepared for scanning electron microscopy. The row of inner hair cells (IHCs) was complete in all animals, while the rows of outer hair cells (OHCs) showed a considerable hair cell loss in some of the animals without a correlation to the change in amplitudes of DPOAE. However, a closer relationship between the decline of amplitudes of DPOAE and the number of missing and changed OHCs (fused stereocilia bundles, missing tip links) could be established. The number of lost OHC does not reflect the decline in DPOAE in all cases. This discrepancy must be considered when the degree of hearing loss needs to be established from changed DPOAE.

The impact of technical conditions of X-ray imaging on reproducibility and precision of digital computer-assisted X-ray radiogrammetry (DXR).

OBJECTIVE: To evaluate the reproducibility of imaging and analysis for bone mineral density (BMD) determination using digital computer-assisted X-ray radiogrammetry (DXR; Pronosco X-posure, version V.2, Sectra Pronosco, Denmark); to verify potential factors that influence BMD extrapolation such as tube voltage, film-focus distance (FFD), film quality and brand (Kodak T-MAT-Plus, Konika SRH, Agfa Scopix), imaging technology (conventional, digital), imaging system (Kodak, Agfa) and exposure level (mAs); and to clarify whether DXR analysis based on printouts of digital images is comparable to analysis of conventional images. DESIGN AND PATIENTS: The hand of a cadaver was X-rayed using varied parameters: 4-8 mAs, 40-52 kV, 90-130 cm FFD. Radiographs under standardised conditions were performed 10 times using a conventional machine (Philips Super 80 CP) and the printouts of a digital system (Digital Diagnost Philips Optimus) for the analysis of reproducibility. One image was scanned and analysed 10 times additionally for imaging reproducibility. RESULTS: Reliability error of the system for the imaging process using conventional radiographs-rays was 0.49% (standard conditions: 6 mAs, 40 kV, 1 m FFD), using printouts of digital images was 2.89% (4 mAs, 42 kV, 1 m FFD) and regarding the analysis process was 0.22%. BMD calculation is not affected by alterations in FFD (precision error 1.21%), mAs (0.83%) or film quality/brand (0.38%), but differs significantly depending on tube voltage (2.70%). The system was not able to analyse conventional images with tube voltages of 49/52 kV. CONCLUSION: DXR technology is stable with most of the tested parameters. Normative data should exclusively be used for calculations using similar tube voltage or correction factors. All other parameters had no significant influence on the BMD calculation. Reproducibility is high. For technical reasons it is not recommended to use the printouts of digital images for BMD determination.

The postoperative stability of the first metatarsal

The hallux valgus deformity is characterised by an increased first intermetatarsal angle, which can be reduced by osteotomies on the first metatarsal bone, such as the Proximal osteotomy and the Scarf shaft osteotomy. Osteotomy and subsequent screw fixations were performed on 18 matched pairs of cadaveric specimens to compare the postoperative stability of these two common types of operative correction. Biomechanical testing with plantar force was carried out and failure load was measured for each specimen. The results indicate that the threaded bones provide a high postoperative loading capacity. When maximal strain was exceeded, the specimens failed in the proximal third, irrespective of the type of osteotomy. Moreover, we found that in contrast to the living age the mineral density and the individual geometry of the bone have a marked influence on the postoperative loading capacity. Finally, static biomechanical studies demonstrated that the Scarf osteotomy is significantly more stable than the commonly used Proximal osteotomy. Regarding the early postoperative mobilization of the patients concerned, the Scarf osteotomy proved to be superior, but the Proximal osteotomy requires a more cautious rehabilitation program (AU)

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Determination of autofluorescence of red blood cells (RbCs) in uremic patients as a marker of oxidative damage.

AIM: It is suggested that the red blood cells (RBCs) of uremic patients have increased oxidative damage. The activities of different antioxidant enzymes and the levels of several antioxidants or lipid peroxidation products in RBCs are usually determined to estimate the oxidative stress in uremia. The autofluorescence of RBCs as measured by flow cytometry is caused by the formation of conjugated Schiff base compounds from aldehydes derived from lipid peroxidation and amino groups of phospholipids or cell proteins, and has been proposed as a marker of oxidative stress. The aim of this study was to evaluate if this method is suitable for estimation of oxidative stress in the RBCs of patients with different degrees of renal insufficiency. PATIENTS AND METHODS: To determine the oxidative damage in RBCs in uremia, the autofluorescence of RBCs was measured by flow cytometry in the following 3 groups of patients: group A: 16 patients with chronic renal failure (CRF); group B: 16 hemodialysis (HD) patients; group C: 16 patients with a well-functioning renal allograft. Twenty-four healthy volunteers served as controls. The basal value of RBC autofluorescence and the autofluorescence of RBCs after oxidative damage by treatment with 0.1 mM hydrogen peroxide (H2O2)/0.7 mM sodium azide were determined. RESULTS: In basal RBC autofluorescence values, no differences were found between the 3 groups and the controls. However, there was a significant correlation between the increase of serum creatinine and RBC autofluorescence in the group of patients with CRF (r = 0.521; p = 0.038). After H2O2 treatment, the RBC autofluorescence rose markedly in all individuals. This increase in RBC autofluorescence was significantly higher in the patients with CRF (p = 0.003) and in the HD patients (p = 0.001) compared to the controls. In contrast, there was no difference in RBC autofluorescence between the patients with renal allograft and the controls after H2O2 treatment. CONCLUSIONS: In conclusion, flow cytometry is a useful tool for determining oxidative damage in RBCs. The RBCs of uremic patients are more susceptible to oxidative damage induced by H2O2, likely caused by diminished antioxidant defense in the RBC membrane. Successful renal transplantation leads to a normal autofluorescence response in the RBCs after H2O2 treatment.

Unusual blood supply to the pancreas by a dorsal pancreatic artery.

A variation of the blood supply to the pancreas was observed in an 89-year-old female, in which the celiac trunk gave off four arteries: the hepatic, splenic, left gastric arteries and an additional dorsal pancreatic artery. One of the branches the dorsal pancreatic artery joined with the superior mesenteric artery to form a longitudinal anastomosis. The anterior and posterior pancreaticoduodenal arcades arose from branches of the superior pancreaticoduodenal and the dorsal pancreatic arteries. The inferior pancreaticoduodenal artery, a branch of the superior mesenteric artery, was missing. The majority of the pancreas was, therefore supplied by the dorsal pancreatic artery. The clinical implications of this finding are that the size, location and course of a dorsal pancreatic artery should be established given its central role in the blood supply to the pancreas observed in the present study.

Pulmonary atresia with hypoplastic right ventricle. A clinical embryological study.

An unusual case of pulmonary atresia with an aberrant karyotype of 46,XX,t(6;8)(p21.2;q11.2) is reported. Fetal ultrasonic examination at the 20th week of gestation revealed a hypoplastic right ventricle and an intact interventricular septum. Authors summarize their postnatal findings in fetal heart and the large adjacent vessels with special reference to the pathogenesis of this rare congenital heart defect. The observation delineates right-ventricular outflow tract obstruction associated with an abnormal pulmonary blood supply. The anatomy of the systemic pulmonary collaterals was studied and correlated with multifocal disorders in the system of the pharyngeal arch arteries in the early embryonic development.

Three-dimensional reconstruction of the anal striated musculature in a human fetus.

Conflicting opinions in the recent literature indicate that the morphological organization and function of the anorectal continence organ has, up to now, not been clearly understood. But a clear imagination of the spatial arrangements of this compound muscle system is of clinical relevance for the pediatric surgeon performing reconstructive surgery. We analyzed 18-microm sections of the pelvic region of 4 human fetuses in order to describe the individual components of this muscle complex. A series of 630 Azan-stained sections was the base for the computer-assisted 3D reconstruction of the levator ani and the external sphincter complex in a male human fetus (14th week p.c.). In this context, special attention was paid to the intermediate muscle layer of the puborectalis which develops ventrally from the funnel-shaped levator ani and joins the tripartite ring system of the sphincter muscle dorsally. Our findings lead to a clear imagination of the spatial arrangement of this intermediate layer and characterize the anorectal muscle complex as an integrated ensemble in which the puborectalis holds a key position.

Zymography with caseogram prints: quantification of pepsinogen.

In caseogram prints, a type of zymogram which is designed for the detection of acid proteases, enzyme activity is detected in an overlay gel of agarose containing skim milk. The use of this technique for protease quantification was investigated in this study using pepsinogen as an example protease. The area of caseogram bands was found to be logarithmically related to protease activity whereas the intensity of the bands was no reliable measure for activity. A reproducible quantification procedure was described. Accuracy and variation were acceptable over a 128-fold range whose lower border was the detection limit (35 pg pepsinogen).

[Scanning electron microscopic findings concerning the formation of the organ of Corti near the helicotrema in guinea pigs]. / Scanningelektronenmikroskopische Befunde zur Ausbildung der Hörhärchen in Helicotremanähe beim Meerschweinchen.

We report on findings in guinea pigs with objectively tested normal hearing ability. At the apical end of the Corti organ only in the inner row of hair cells the stereociliae are detectable by scanning electron microscopy. Here the row is interrupted several times. Near the helicotrema we find first the inner row of the outer hair cells, then the middle row and finally the outer row. At the beginning of the D-turn their arrangement is disordered. Normally, at the basal end of the D-turn all rows of inner and outer hair cells show their typical formation. This finding should be taken into consideration when making a cochleogram for proving of experimental noise damages.

Effects of industrial noise exposure on distortion product otoacoustic emissions (DPOAEs) and hair cell loss of the cochlea--long term experiments in awake guinea pigs.

Distortion product otoacoustic emissions (DPOAEs), a sensitive detector of outer hair cell (OHC) function, cochlear microphonics (CM), and hair cell loss have been monitored in 12 awake guinea pigs before and after 2 h exposure to specific, played-back industrial noise (105 dB SPL maximal intensity). All animals had stable DPOAE levels before noise exposure. In the first hours after noise exposure DPOAE levels were reduced significantly. In about 70% a partial recovery of the DPOAEs was found within 4 months after noise exposure. In 16% of the investigated ears no recovery of DPOAEs was observed. However, in a few ears increased DPOAEs were observed after noise exposure. Exposure to industrial noise caused both morphological changes in the middle turns of the cochlea and electrophysiological changes in the middle frequency range. A close correlation existed between reduced DPOAE levels, loss in CM potentials, and area of damaged or lost OHCs, but not with the numbers of damaged or lost OHCs in the cochlea. It can be concluded that continuous industrial noise causes a damage to OHCs which differs form the damage caused by impulse noise.

Hemolysis of human erythrocytes with saponin affects the membrane structure.

Incubation of cells and tissues with saponin makes the lipid bilayer permeable to macromolecules. Ghosts (membrane preparations) of saponin-lysed erythrocytes do not reseal, thus indicating an irreversible damage of the lipid bilayer. We investigated the influence of disturbance of the lipid bilayer on membrane proteins by comparing ghosts of saponin-lysed erythrocytes with ghosts of cells lysed in hypotonic buffer. Transmission electron microscopy revealed destruction of the lipid bilayer and emergence of multilamellar buds in saponin-lysed ghosts. Freeze-fracture electron microscopy showed regions with crystalline lipids and an increase in particle-free areas on fracture faces. The number of protein sulfhydryl groups and the binding of hemoglobin were diminished in saponin-lysed ghosts. A Scatchard plot of hemoglobin binding revealed the decrease of high affinity binding sites. All these results indicate an aggregation of band 3 protein also demonstrated by laser scanning microscopy after incubation of cells labelled with eosin-5-maleimide with sublytic concentration of saponin. Hemolysis with saponin also affected the interaction between transmembrane proteins and the cytoskeleton. Dissociation of peripheral membrane proteins by incubation of ghosts in low salt buffer or by blocking sulfhydryl groups was increased and the association of spectrin with spectrin-depleted vesicles was decreased. The increased incorporation of the fluorescent probe Merocyanine 540 into saponin-lysed ghosts and the increased relative fluorescence quantum yield confirmed the perturbation of the lipid bilayer and the changed interaction between membrane lipids and intrinsic membrane proteins. Our results suggest that permeabilization of the lipid bilayer with saponin to admit the access of antibodies to the cytoplasmic surface of cells can aggregate transmembrane proteins and affect the immunocytochemical localization of associated proteins of the cytoskeleton.

Separation of the intracellular secretory compartment of rat liver and isolated rat hepatocytes in a single step using self-generating gradients of iodixanol.

A novel method is described for the separation on a single gradient of the major intracellular organelles of the secretory pathway, the Golgi, the smooth endoplasmic reticulum, and the rough endoplasmic reticulum. Total microsomes were prepared from rat liver by differential centrifugation and resuspended in 20% iodixanol. The microsomal suspension was then layered between a 30% iodixanol cushion and a layer of 15% iodixanol and centrifuged in a vertical rotor for 2 h. The microsomes distributed in four visible bands. The gradients were collected by upward displacement and were characterized (i) by determination of UDP galactose-galactosyltransferase (Golgi marker) NADPH-cytochrome c reductase (endoplasmic reticulum marker) and RNA (rough endoplasmic reticulum marker); (ii) by immunoblotting for TGN38 (trans-Golgi marker) and GS28 (cis-Golgi marker) and for protein disulfide isomerase (endoplasmic reticulum lumenal marker); (iii) by determination of the lipid composition; and (iv) by electron microscopy. The results suggest that the top band (density 1.045-1. 090 g/ml), which contains 68% of the galactosyltransferase activity, consists of vesicles derived from the Golgi. The second broad band in the middle of the tube (density 1.130-1.160 g/ml), which contains 54% of the NADPH-cytochrome c reductase activity, consists mainly of vesicles derived from the smooth endoplasmic reticulum, overlapped at the top by a small band of Golgi-derived lamellae. The two bands at the bottom of the tube (density 1.130-1.160 and density 1.180-1. 220 g/ml) appear to contain two subfractions of vesicles derived from the rough endoplasmic reticulum.

The granulated convoluted tubules of the rat submandibular glands under experimental conditions.

Granulated convoluted tubules are the specific ductal segment of the submandibular glands of mice and rats. These tubules are functionally integrated into hormonal circuits, produce regulatory peptides as well as epidermal and nerve growth factor. The experimental studies on adult male Wistar and Fischer 344 rats demonstrate acute cytotoxic lesions of the granulated tubules by means of a single dose of 2-acetylaminofluorene. After only a few administrations of the compound the intralobular duct tree is lined by an atrophic epithelium with loss of specific structures, the EGF immunoreactivity and the susceptibility to further cytolethal effects. The early selective damage of the granulated convoluted tubules indicates that the growth factor production and certain drug-metabolizing/drug-excreting capacities are situated within the same ductal segment. It is considered that other systemically administered compounds might also influence this growth factor-producing ductal segment, though less dramatically than 2-acetylaminofluorene.

Ciprofibrate--racemate and enantiomers: effects of a four-week treatment on male inbred Fischer rats. A biochemical and morphological study.

Ciprofibrates (racemate and both enantiomers, Raccip, R- and Scip) were administered orally in doses of 1 and 10 mg/kg once daily over 28 days to male inbred Fischer 344 rats, age 90-110 days at the beginning of the experiment. Body mass gain was observed in all groups. The 1 mg groups showed almost no difference to the control group. The 10 mg groups exhibited less body mass gain, most pronounced in the Scip group. Liver masses were increased in a dose dependent manner up to more than 200%, only the 10 mg Scip group was not significantly different from the 1 mg group which exhibited an increase in liver weight to about 175%. Also the kidney weights increased to 130%, whereas thymus and spleen weights were decreased in the high dose groups. Liver microsomal cytochromes P450 (P450) concentrations were not altered in the 1 mg groups and distinctly lowered in the 10 mg groups. Ethoxyresorufin and ethoxycoumarin O-deethylations were lowered in all experimental groups in a dose dependent manner, after administration of the high doses down to 30% of the control levels or less. Pentoxyresorufin O-depentylation, however, was increased in all 1 mg groups. In the high dose groups it was not altered. Ethylmorphine N-demethylation was decreased after administration of the high doses by about 50%, but only Scip decreased this reaction also after administration of the low dose. NADPH/Fe2+-stimulated microsomal luminol and lucigenin amplified chemiluminescence was increased, whereas hydrogen peroxide formation was depressed even by the low doses to 50% of the normal values, to about 25% by the high doses. Microsomal lipid peroxidation, however, was only slightly or not influenced. Glutathion concentrations (in the reduced and the oxidized form) were increased in a dose dependent manner by about 20 to 30%, the concentration of lipid peroxides was not significantly influenced. Thus, the effects of the enantiomers were not different and were similar to those of the racemate. In serum, cholesterol and triglycerides were only moderately lowered. Albumin concentrations were significantly enhanced in all groups, total proteins after 1 mg/kg Raccip only. Serum bilirubins were not altered, and among the indicator enzymes for liver damage only ALAT, alkaline phosphatase and the dehydrogenases were increased, in no case higher than twofold. Histologically distinct effects were seen after administration of both doses, more pronounced after 10 mg/kg, but with no differences between the enantiomers and Raccip: marked hypertrophy of the hepatocytes, reduced staining of the nuclei, strongly acidophilic granulated cytoplama, no basophilia of the cell bodies, loss of glycogen. These changes were most pronounced around the central veins. Hepatocyte apoptoses also were observed. By immunohistochemistry an increased staining was seen for all P450 isoforms tested (1A1, 2B1, 2E1, 3A2 and 4A1), predominantly perivenously and most pronounced after administration of the high doses without differences between Rcip, Scip or Raccip (preliminary results). By electron microscopy a moderate proliferation of peroxisomes after treatment with 1 mg/kg Cips with a ratio between mitochondria and peroxisomes of about 1:1 (controls: 10:1) was observed, and the peroxisomes were a more heterogeneous population. The relative portions of glycogen and both forms of the ER decreased. Treatment with 10 mg/kg Rcip, Scip or Raccip led to a strong increase in the number of peroxisomes, in some hepatocytes the ratio between mitochondria and peroxisomes was 1:3 with an increased heterogeneity among the peroxisomes evidenced by a broad range of electron densities. Most peroxisomes lacked a nucleoid. Thus, the biochemical effects differed only slightly and the morphological effects of the enantiomers were not different and were similar to those of the racemate.

2-Acetylaminofluorene-produced selective cytotoxic damage of a ductal compartment and its repair in the submandibular gland of rats.

Salivary glands of rodents are rarely affected with spontaneous and induced malignancies. This may be linked with low physiologic cell renewal and the infrequency of cytolethal actions by xenobiotics. The genotoxic 2-acetylaminofluorene, carcinogenic for other organs, causes acute damage in salivary ducts. In the submandibular glands the damage is limited to the granulated convoluted tubules. They produce and release regulatory peptides including epidermal growth factor and nerve growth factor. The partial chemical sialoadenectomy is repaired by sequential cell proliferation in the basal cell layer of interlobular ducts and in dilated intralobular ducts (day 4 and 6), in intermediate duct-like structures (day 6 and 8), and lastly in acini (day 8 and 12). This is associated with a transient loss of structural characteristics of striated ducts and acini (up to day 6) and of the immunoreactivity for S-100 protein (up to day 4). Actin immunoreactivity at the acinar base is increased from day 6 to 20. Analogous to the late postnatal differentiation of the granulated convoluted tubules, their structural characteristics and immunoreactivity for epidermal growth factor do not recover within 20 days. The acute lesion of the endocrine ductal segment is suggested to be causally involved with other systemic effects following treatment with 2-acetylaminofluorene. First, hypophagia with loss of body, liver and thymus weight may result from disturbed saliva production. Second, previous studies have shown a mitotic burst of the biliary epithelium and bloodborne lymphocyte-stimulating activities. Either effect could be brought about by regulatory peptides (see above), probably after elevated circulatory release from necrotic granulated convoluted tubules.

Flow cytometric analysis of band 3 protein of human erythrocytes.

Flow cytometry was used to quantify the transmembrane anion exchanger (band 3 protein) of human erythrocytes by covalently bound eosin-5-maleimide. In vitro and in vivo vesiculated red blood cells were investigated. The fluorescence and light scatter signals of cells after heat induced vesiculation, in vivo ageing, and in patients with hereditary spherocytosis were decreased. These results reflect a deficiency of band 3 protein which is presumably caused by membrane surface area loss. It was possible to distinguish control erythrocytes, erythrocytes from patients with hereditary spherocytosis, and from other forms of haemolytic anaemias on the basis of their light scatter and fluorescence signals characteristics.

Is the brush border membrane of the intestinal mucosa a generator of "chymosomes"?

1. The microvilli of enterocytes in calf intestine demonstrate high levels of vesiculation activity at the top and at the basal region. 2. The morphology of the vesicles associated with microvilli (100-500 nm diameter, unilamellar, few intramembraneous particles, high AP activity) is very similar to the morphology of vesicles found in the chyme. 3. Vesicles can be purified 6-10 fold from chyme of the calf intestine applying a Mg(++)-precipitation method, used for brush border membrane preparation. 4. Specific activities of alkaline phosphatase and disaccharidases were found to be much higher in chyme vesicles than in the mucosa. 5. Phospholipid content and phospholipid composition is in chyme vesicles different from brush border membrane vesicles. 6. The characterized chyme vesicles are referred to as chymosomes. We consider the mucosa as a large-scale generator of chymosomes, i.e. digestive enzymes bearing vesicles.

Dysmorphic erythrocytes in glomerulonephritis. 1. Electron microscopical and histochemical investigation.

Dysmorphic erythrocyte malformation in urine is characteristic of glomerulonephritis. The mechanisms leading to this phenomenon are still unknown. To obtain evidence of the site as well as of the process of erythrocyte damage, electron microscopical and histochemical investigations of renal biopsy materials from 19 patients with histologically defined glomerulonephritis were performed. The results suggest that the initial damage of erythrocytes in the glomerular area is reasoned by enzymatic glycocalyx destruction. On passage through the tubular system the osmotically sensitized surface altered cells undergo rapid hemolysis and losses of membrane skeletal proteins leading to dysmorphic shape transformations.

Bay Y 3118, a new quinolone derivative, rapidly eradicates Listeria monocytogenes from infected mice and L929 cells.

Bay Y 3118 is a new quinolone derivative with pronounced activity against gram-positive bacteria including the facultatively intracellular bacterium Listeria monocytogenes. Bay Y 3118 was tested in vitro and in animal models of listeriosis. All strains of L. monocytogenes and other Listeria spp. were highly susceptible in vitro; the MICs for these organisms ranged from 0.062 to 0.25 micrograms/ml. Bay Y 3118 was rapidly bactericidal in vitro, with a postantibiotic effect occurring for 3 h after removal of the antibiotic. L. monocytogenes was eliminated from infected L929 cells treated with Bay Y 3118, suggesting a bactericidal effect on the listeriae in these cells. Immunocompetent mice were rapidly cured by treatment with 4 mg every 12 h. Concomitantly, the levels of interleukin 6 and gamma interferon in mouse sera declined rapidly. In immunocompetent mice, treatment with 2 mg of Bay Y 3118 every 12 h resulted in a greater initial reduction in the listerial counts in the organs than treatment with 2 mg of ampicillin every 12 h. Bay Y 3118 completely eliminated L. monocytogenes from the livers and spleens of chronically infected nude mice. However, some of the bacteria reappeared after the cessation of therapy. In conclusion, Bay Y 3118 is an excellent candidate substance for the therapy of infections caused by facultatively intracellular gram-positive bacteria such as L. monocytogenes.