Spin- and angle-resolved photoemission spectroscopy study of heptahelicene layers on Cu(111) surfaces.

It has been demonstrated previously that electrons interact differently with chiral molecules depending on their polarization. For enantiomeric pure monolayers of heptahelicene, opposite asymmetries in spin polarization were reported and attributed to the so-called chirality-induced spin selectivity effect. However, these promising proof-of-concept photoemission experiments lack the angular and energy resolution that could provide the necessary insights into the mechanism of this phenomenon. In order to fill in the missing gaps, we provide a detailed spin- and angle-resolved photoemission spectroscopy study of heptahelicene layers on a Cu(111) substrate. Throughout the large accessible energy and angle range, no chirality induced spin asymmetry in photoemission could be observed. Possible reasons for the absence of signatures of the spin-dependent electron transmission through the chiral molecular layer are briefly discussed.

[Orbital complications]. / Orbitale Komplikationen.

A disease or symptom of disease spreading from the vicinity of the orbit to the internal structures of the orbit is referred to as an orbital complication. Orbital complications can have a traumatic, inflammatory, allergic, or autoimmunologic cause. They are more frequent in children than adults. The present review aims to provide a description of orbital complications, their etiology, pathogenesis, and treatment. Recent literature in the field is acknowledged and discussed, and results from the authors' own patient groups are analyzed. Particular attention is paid to orbital complications due to acute sinusitis and those caused by acute hemorrhage. The term "orbital phlegmon" frequently used for orbital complications with inflammatory causes is confusing and should be replaced by differentiated grading. Diagnosis and treatment of orbital complications requires interdisciplinary collaboration, whereby inclusion of ophthalmologists is particularly important. Treatment of orbital complications depends on their cause. In inflammatory cases affecting only the preseptal tissues and compartment, conservative therapy is indicated. If clinical findings worsen within 24 h of conservative therapy, or if the patient presents with a high-grade orbital complication with loss of visual acuity or impairment of globe mobility, surgery is required. In cases of acute hemorrhage into the orbit, a procedure for decreasing intra-orbital pressure is mandatory (i. e., canthotomy, cantholysis, orbital decompression).

[Orbital decompression : Indications, technique, results]. / Orbitadekompression : Indikationen, Operationstechnik, Ergebnisse.

Orbital decompression is an effective surgical procedure to reduce intraorbital pressure. Causes may diseases leading to rapid pressure increases, e. g., bleedings, and those causing slower, progressive pressure increases, e. g., tumors or Graves' orbitopathy. During fat tissue decompression, peri- and retrobulbar adipose tissue is removed; in bony decompression, one or more bony orbital walls are removed (one-, two-, or three-wall decompression). In many cases the procedures are combined. Recent developments are the transconjunctival approaches for removing parts of bony orbital walls. Complications include double vision, which occurs in up to 30% of cases depending on the approach, hemorrhage, infections, development of chronic sinusitis, and iatrogenic skull base lesions with consecutive meningitis. In the hands of an experienced rhino- and head and neck surgeon, the intervention has low complication rates.

[Lateral Sinus Thrombosis--A Rare Complication of an Acute Mastoiditis or Infected Cholesteatoma]. / Die Sinusvenenthrombose--eine seltene Komplikation der akuten Mastoiditis und des Cholesteatoms.

BACKGROUND: Lateral sinus thrombosis (LST) is a rare but threatening complication of an acute mastoiditis or infected cholesteatoma. Currently only very few papers are available in the literature dealing with the systematic investigation of patients with suspected LST. The purpose of the present study was to evaluate the clinical, intraoperative and therapeutic findings of patients with particular disease. PATIENTS AND METHODS: For this retrospective study the clinical records of 7 patients which were admitted for a suspected LST were evaluated. All patients underwent mastoidectomy with exposition of the lateral sinus and investigating of its blood flow. RESULTS: A LST was confirmed in 4 patients, 3 patients had a phlebitis. Patients with a LST presented additional symptoms beside otalgia, i. e., dizziness, cephalgia, meningism, deafness of the affected ear, and facial nerve paresis. Postoperative MRI scans revealed a recanalization of the sinus in all cases. Although immediate surgery, 2 patients developed a 2-staged brain abscess in the cerebellum. CONCLUSION: Clinical symptoms of the SVT are unspecific. In cases of an acute mastoiditis, neurological signs might be pathognomonic and can direct to a LST. Therapeutic concepts comprise intravenous antibiotics and operative elimination of disease. The exposition of the lateral sinus should be performed in any mastoidectomy for a LST in order to scrutinize its blood flow. In case of a thrombosis additional anticoagulative therapy might be indicated. To exclude a 2-staged brain abscess control MRI scans 7 through 14 days postoperatively are recommended.

[Pilomatrixoma - an important differential diagnosis of facial masses]. / Das Pilomatrixom - eine wichtige Differenzialdiagnose von Raumforderungen der Kopf- und Gesichtshaut.

BACKGROUND: Pilomatrixoma are rare tumors usually arising from the sebaceous glands in the subcutaneous tissue. They are the most frequent superficially localized tumors of the cheek and parotid region in children. About 20% of all tumors in this area in children are pilomatrixoma. Currently there are only a few studies in the literature which describe characteristic findings in these tumors. The purpose of the present study was to describe clinical, sonographical and morphological characteristics of these rare tumors. PATIENTS AND METHODS: Clinical records of 6 patients which were operated on for a pilomatrixoma were retrospectively analyzed. All tumors were completely excised followed by an histopathological examination on H&E stained specimens. RESULTS: All patients reported about a slowly growing painless mass in the parotid area or nuchal. Sonographically tumors displayed as hyperechoic masses with a dorsal sound extinction, due to hypercalcification. Histopathologically all tumors were characterized by typical basaloid and ghost cells, accompanied by a foreign-body reaction. CONCLUSION: Pilomatrixoma are an important differential diagnosis of unclear masses in the head and neck especially in children. The sonographical characteristics are variable and unspecific. A fine-needle aspiration biopsy is not recommended, since false malignant cytologic findings occur quite often. Therapeutically complete excision is required. Usually no adjuvant therapy is necessary, and the prognosis is good.

Caffeine does not attenuate experimentally induced ischemic pain in healthy subjects.

BACKGROUND AND AIMS: Caffeine is likely the most widely used psychoactive substance in the world. It is also an analgesic adjuvant and has individual analgesic properties. The latter effect has been attributed to adenosine receptor antagonism, but the site of action is unknown. The aim of this study was to investigate the analgesic properties of caffeine on experimentally induced ischemic pain and to attempt to elucidate whether the site of action is central or peripheral. MATERIALS AND METHODS: Seventeen healthy subjects received intravenous (i.v.) regional and systemic infusions of caffeine at 10 mg/kg or placebo in a double-blind, crossover fashion to investigate the site of action for caffeine-induced analgesia. Subjects underwent a sub-maximum effort tourniquet test. Pain scores [visual analogue scale (VAS), 0-100] were assessed every minute up to a maximum of 45 min. RESULTS: The sum of pain scores (SPS, accumulation of VAS scores) was attenuated neither by systemic 2405 (+/-234) nor by i.v. regional caffeine 2427 (+/-190) as compared with placebo 2442 (+/-205), P=0.99 (mean+/-SEM). Time to maximal VAS score did not differ significantly between treatments, P=0.94. There was no correlation between caffeine concentration in plasma and time to maximal pain score, or between SPS and plasma concentration. CONCLUSION: Caffeine does not have an analgesic effect on ischemic pain, either by a peripheral or by a central site of action.

[Disabled elderly people waiting for institutionalization to a hospital ward: prospective study in the administrative district of Strasbourg (France)]. / Personnes âgées dépendantes en attente d'entrée en EHPAD depuis un service hospitalier: étude prospective sur la communauté urbaine de Strasbourg, France.

OBJECTIVES: Our aim was to estimate the number of non-satisfied instutionalization requests for inpatients and to describe the strategies elaborated to compensate for the waiting time. METHODS: This prospective follow-up study concerning all requests for institution admission for inpatients aged 75 years or older hospitalized in acute care and rehabilitation wards. Descriptive data were gathered throughout the social support process conducted during the hospitalization. A three months follow-up was conducted. RESULTS: Among 5200 hospitalizations, a social support process was initiated for 270 patients aged 75 years and over. Two thirds of the sample were women (n=163). Mean age was 82 years. Fifty-two percent of the subjects met the criteria for iso-resource grades (IRG) 1 to 2 and 90% in IRG 1 to 4. The mean length of hospitalized stay (MLOS) was 56.8+/-10.2 days; the MLOS of unjustified stay of 23.5+/-5.6 (n=222). The average time before the social worker was informed of the patient's situation was 13.6+/-2.0 days; in addition, the time required to establish the administrative documents necessary for initiation of the social support progress was 15.0+/-1.8. The principal reasons for social support were physical dependence (77%), mental dependence (60%), insufficient family support (36%) and/or disease progression (21%). At three months, 104 patients were institutionalized, 128 were still on institution waiting list (in hospital: 48%; at home: 16%) and 38 had died (14%). The estimated annual institutional deficit for disabled elderly people was 512 beds. CONCLUSION: In light of demographical perspectives, an overall re-organization of the geriatric network is absolutely necessary. A simple increase in the capacity to fulfil the institutional beds deficit would be insufficient.

Stable expression of the vesicular GABA transporter following photothrombotic infarct in rat brain.

Before exocytotic release of the inhibitory neurotransmitter GABA, this amino acid has to be stored in synaptic vesicles. Accumulation of GABA in vesicles is achieved by a specific membrane-integrated transporter termed vesicular GABA transporter. This vesicular protein is mainly located at presynaptic terminals of GABAergic interneurons. In the present study we investigated the effects of focal ischemia on the expression of the vesicular GABA transporter. Vesicular GABA transporter mRNA and protein expression was examined after photothrombosis in different cortical and hippocampal brain regions of Wistar rats. In situ hybridization and quantitative real-time RT-PCR were performed to analyze vesicular GABA transporter mRNA. Both vesicular GABA transporter mRNA-stained perikarya and mRNA expression levels remained unaffected. Vesicular GABA transporter protein-containing synaptic terminals and somata were visualized by immunohistochemistry. The pattern of vesicular GABA transporter immunoreactivity as well as the protein expression level revealed by semiquantitative image analysis and by Western blot remained stable after stroke. The steady expression of vesicular GABA transporter mRNA and protein after photothrombosis indicates that the exocytotic release mechanism of GABA is not affected by ischemia.

Mapping of binding domains of nontypeable Haemophilus influenzae HMW1 and HMW2 adhesins.

Nontypeable Haemophilus influenzae is an important cause of localized respiratory tract disease, which begins with colonization of the upper respiratory mucosa. In previous work we reported that the nontypeable H. influenzae HMW1 and HMW2 proteins are high-molecular-weight nonpilus adhesins responsible for attachment to human epithelial cells, an essential step in the process of colonization. Interestingly, although HMW1 and HMW2 share significant sequence similarity, they display distinct cellular binding specificities. In order to map the HMW1 and HMW2 binding domains, we generated a series of complementary HMW1-HMW2 chimeric proteins and examined the ability of these proteins to promote in vitro adherence by Escherichia coli DH5alpha. Using this approach, we localized the HMW1 and HMW2 binding domains to an approximately 360-amino-acid region near the N terminus of the mature HMW1 and HMW2 proteins. Experiments with maltose-binding protein fusion proteins containing segments of either HMW1 or HMW2 confirmed these results and suggested that the fully functional binding domains may be conformational structures that require relatively long stretches of sequence. Of note, the HMW1 and HMW2 binding domains correspond to areas of maximal sequence dissimilarity, suggesting that selective advantage associated with broader adhesive potential has been a major driving force during H. influenzae evolution. These findings should facilitate efforts to develop a subcomponent vaccine effective against nontypeable H. influenzae disease.

Nociceptin/orphanin FQ in spinal nociceptive mechanisms under normal and pathological conditions.

Nociceptin and its receptor are present in dorsal spinal cord, indicating a possible role for this peptide in pain transmission. The majority of functional studies using behavioral and electrophysiological studies have shown that nociceptin applied at spinal level produces antinociception through pre- and post-synaptic mechanisms. The spinal inhibitory effect of nociceptin is not sensitive to antagonists of opioid receptors such as naloxone. Thus, nociceptin-induced antinociception is mediated by a novel mechanism independent of activation of classic opioid receptors. This has raised the possibility that agonists of the nociceptin receptor may represent a novel class of analgesics. Supporting this hypothesis, several groups have shown that intrathecal nociceptin alleviated hyperalgesic and allodynic responses in rats after inflammation or partial peripheral nerve injury. Electrophysiological studies have also indicated that the antinociceptive potency of spinal nociceptin is maintained or enhanced after nerve injury. It is concluded that the predominant action of nociceptin in the spinal cord appears to be inhibitory. The physiological role of nociceptin in spinal nociceptive mechanisms remains to be defined. Moreover, further evaluation of nociceptin as a new analgesic calls the development of non-peptide brain penetrating agents.

The effect of intrathecal endomorphin-2 on the flexor reflex in normal, inflamed and axotomized rats: reduced effect in rats with autotomy.

Endomorphin-2, a newly discovered endogenous opioid peptide and agonist at the mu-opioid receptor, was injected intrathecally in normal rats and animals with unilateral peripheral inflammation or sciatic nerve section and its effect on the nociceptive flexor reflex was analysed. In normal rats, intrathecal endomorphin-2 induced a strong and dose-dependent depression of the reflex, which was naloxone-reversible. The effect of intrathecal endomorphin-2 was fairly brief, lasting for about 20-30 min at the highest dose, 4 microg. The effect of endomorphin-2 in inflamed rats was not significantly different from that in normals. After nerve section some rats developed autotomy behavior. In these rats endomorphin-2 had significantly reduced effect. However, the reflex depressive effect of intrathecal endomorphin-2 was unchanged in axotomized rats without autotomy. It is suggested that intrathecal endomorphin-2 has antinociceptive effect in the rat spinal cord under normal and inflammatory conditions. After peripheral nerve injury the sensitivity to endmorphin-2 may be reduced in rats that exhibit ongoing neuropathic pain-like behaviors.

Maturation and secretion of the non-typable Haemophilus influenzae HMW1 adhesin: roles of the N-terminal and C-terminal domains.

Non-typable Haemophilus influenzae is a common cause of human disease and initiates infection by colonizing the upper respiratory tract. The non-typable H. influenzae HMW1 and HMW2 adhesins mediate attachment to human epithelial cells, an essential step in the process of colonization. HMW1 and HMW2 have an unusual N-terminus and undergo cleavage of a 441-amino-acid N-terminal fragment during the course of their maturation. Following translocation across the outer membrane, they remain loosely associated with the bacterial surface, except for a small amount that is released extracellularly. In the present study, we localized the signal sequence to the first 68 amino acids, which are characterized by a highly charged region from amino acids 1-48, followed by a more typical signal peptide with a predicted leader peptidase cleavage site after the amino acid at position 68. Additional experiments established that the SecA ATPase and the SecE translocase are essential for normal export and demonstrated that maturation involves cleavage first between residues 68 and 69, via leader peptidase, and next between residues 441 and 442. Site-directed mutagenesis revealed that HMW1 processing, secretion and extracellular release are dependent on amino acids in the region between residues 150 and 166 and suggested that this region interacts with the HMW1B outer membrane translocator. Deletion of the C-terminal end of HMW1 resulted in augmented extracellular release and elimination of HMW1-mediated adherence, arguing that the C-terminus may serve to tether the adhesin to the bacterial surface. These observations suggest that the HMW proteins are secreted by a variant form of the general secretory pathway and provide insight into the mechanisms of secretion of a growing family of Gram-negative bacterial exoproteins.

Effects of intrathecal orphanin FQ on a flexor reflex in the rat after inflammation or peripheral nerve section.

We examined the effects of intrathecal orphanin FQ, the endogenous ligand for the orphan opioid-like receptor, on the hamstring nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats after carrageenan-induced inflammation or unilateral sciatic nerve transection. As described previously [Xu, X.-J., Hao, J.-X., Wiesenfeld-Hallin, Z., 1996. Orphanin FQ or antiorphanin FQ: potent spinal antinociceptive effect of orphanin FQ/orphanin FQ in the rat. NeuroReport 7, 2092-2094.], intrathecal orphanin FQ induced a dose-dependent depression of the flexor reflex with a ED50 of 965 ng. Initial reflex facilitation was noted in some experiments at lower doses (10 or 100 ng). A similar bi-phasic response pattern to intrathecal orphanin FQ was observed in experiments conducted in inflamed or axotomized rats. However, the magnitude of the initial reflex facilitation was significantly increased in inflamed rats compared to normals whereas the duration of reflex depression was significantly shortened. The ED50 for reflex depression was 2.4 jig for inflamed rats. In contrast, axotomy did not significantly alter the facilitatory and depressive effect of orphanin FQ with ED50 for reflex depression being 374 ng. These results confirmed an inhibitory action of orphanin FQ on spinal nociception in rats. It is suggested that the effect of orphanin FQ may be modulated by inflammation and nerve injury. In particular, unlike morphine, there seems to be no reduction in the effect of spinal orphanin FQ in inducing antinociception after peripheral nerve axotomy.

On the role of galanin in mediating spinal flexor reflex excitability in inflammation.

The effects of exogenous and endogenous galanin on spinal flexor reflex excitability was evaluated in rats one to eight days after the induction of inflammation by subcutaneous injection of carrageenan into the sural nerve innervation area. In normal rats, electrical stimulation of C-fibres in the sural nerve elicited a brisk reflex discharge. Conditioning stimulation of C-fibres (1/s) generated a gradual increase in reflex magnitude (wind-up), which was followed by a period of reflex hyperexcitability. Intrathecal galanin dose-dependently blocked reflex hyperexcitability induced by C-fibre conditioning stimulation whereas i.t. M-35, a high-affinity galanin receptor antagonist, moderately potentiated this effect. At one to three days after the injection of carrageenen, when inflammation was at its peak, the magnitude of the reflex was significantly increased and discharge duration became prolonged. However, wind-up and reflex hyperexcitability were significantly reduced. Furthermore, reduced reflex excitability during conditioning stimulation ("wind-down") and depression of the reflex were sometimes present, which are rarely observed in normal rats. Intrathecal galanin reduced hyperexcitability during inflammation, although its potency was weaker than in normals. However, the galanin receptor antagonist M-35 strongly enhanced wind-up and reflex hyperexcitability, similarly as in normal rats. The baseline flexor reflex, wind-up and C-fibre conditioning stimulation-induced facilitation were normalized four to eight days after carrageenan injection when signs of inflammation were diminishing. Interestingly, intrathecal galanin and M-35 failed to influence spinal excitability. The results suggest a complex functional plasticity in the role of endogenous galanin in mediating spinal excitability during inflammation. There appears to be an enhanced endogenous inhibitory control by galanin on C-afferent input during the peak of inflammation, which may explain the relative ineffectiveness of exogenous galanin. During the recovery phase there may be a reduction in galanin receptors, which may impair the action of endogenous and exogenous galanin. These results further support the notion that galanin is an endogenous inhibitory peptide in nociception.

Secretion of the Haemophilus influenzae HMW1 and HMW2 adhesins involves a periplasmic intermediate and requires the HMWB and HMWC proteins.

Non-typable Haemophilus influenzae is a common cause of human disease and initiates infection by colonizing the upper respiratory tract. The non-typeable H. influenzae HMW1 and HMW2 non-pilus adhesins mediate attachment to human epithelial cells, an essential step during colonization. In order to facilitate interaction with host cells, HMW1 and HMW2 are localized on the surface of the organism in a process that involves cleavage of a 441-amino-acid N-terminal fragment. In the present study, we investigated the pathway for the secretion of HMW1 and HMW2. Cell fractionation experiments and cryoimmunoelectron microscopy demonstrated that a periplasmic intermediate occurs, suggesting involvement of the Sec machinery. Additional analysis revealed that, ultimately, the proteins are partially released from the surface of the organism. Studies with Escherichia coli harbouring plasmid subclones extended earlier findings and suggested that the secretion of HMW1 requires accessory proteins designated HMW1B and HMW1C, while the secretion of HMW2 requires proteins called HMW2B and HMW2C. Further analysis established that HMW1B/HMW1C and HMW2B/HMW2C are interchangeable, an observation consistent with the high degree of homology between HMW1B and HMW2B and between HMW1C and HMW2C. Additional studies of the hmw1 locus indicated that HMW1B is located in the outer membrane and serves to translocate HMW1 across the outer membrane. In the absence of HMW1B, HMW1 remains unprocessed and is degraded in the periplasmic space, at least in part by the DegP protease. Mutagenesis of an HMW1 N-terminal motif shared with other secreted proteins resulted in diminished processing and extracellular release, suggesting interaction of this motif with the HMW1B protein. Continued investigation of the HMW1 and HMW2 adhesins may provide general insights into protein secretion and bacterial pathogenesis.

Characterization of a transposon Tn916-generated mutant of Haemophilus ducreyi 35000 defective in lipooligosaccharide biosynthesis.

To define the role of the surface lipooligosaccharide (LOS) of Haemophilus ducreyi in the pathogenesis of chancroid, Tn916 mutants of H. ducreyi 35000 defective in expression of the murine monoclonal antibody (MAb) 3F11 epitope on H. ducreyi LOS were identified by immunologic screening. One mutant, designated 1381, has an LOS which lacks the MAb 3F11 epitope and migrates with an increased mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The gene disrupted by the Tn916 element in strain 1381 was identified by cloning the sequences flanking the Tn916 element. The sequences were then used to probe a lambda DASHII genomic library. In strain 1381, Tn916 interrupts a gene which encodes an open reading frame (ORF) with an Mr of 40,246. This ORF has homology to the product of the rfaK gene of Escherichia coli. The major LOS glycoform produced by strain 1381 was analyzed by using a combination of mass spectrometry, linkage and composition analysis, and 1H nuclear magnetic resonance spectroscopy. The major LOS species was found to terminate in a single glucose attached to the heptose (L-glycero-D-manno-heptose, or Hep) trisaccharide core. In the wild-type strain 35000, glucose serves as the acceptor for the addition of the D-glycero-D-manno-heptose (or DDHep), which extends to form the mature branch of the H. ducreyi LOS. This mature oligosaccharide is in turn partially capped by the addition of sialic acid (NeuAc), i.e., NeuAc2 alpha-->3Gal beta1-->4GlcNAc beta1-->3Gal beta1-->4DDHep alpha1-->6Glc beta1 (W. Melaugh et al., Biochemistry 33:13070-13078, 1994). Since this LOS terminates prior to the addition of the branch DD-heptose, this gene is likely to encode the D-glycero-D-manno-heptosyltransferase. Strain 1381 exhibits a significant reduction in adherence to and invasion of primary human keratinocytes. This defect was complemented by the cloned heptosyltransferase gene, indicating that the terminal portion of the LOS oligosaccharide plays an important role in adherence to human keratinocytes.

Effect of lipid modification on the physicochemical, structural, antigenic and immunoprotective properties of Haemophilus influenzae outer membrane protein P6.

The outer membrane lipoprotein, P6 of Haemophilus influenzae was studied to determine the importance of the native palmitoyl moiety on its physicochemical and immunological properties. A recombinant P6 (rP6) molecule devoid of lipidation signal sequence was expressed in Escherichia coli and its properties were compared to those of the palmitylated protein purified from H. influenzae. The isoelectric point of rP6 was more acidic than that of the native protein and also exhibited less secondary structure than P6 as judged by circular dichroism. However, both forms of P6 induced identical P6-specific antibody titers in guinea pigs when Freund's adjuvant was used. These antisera reacted with a panel of overlapping P6 peptides in a comparable manner and in addition, rabbit antisera raised against the P6 peptides reacted equally well with P6 and rP6. Furthermore, all human convalescent sera tested exhibited similar anti-P6 and anti-rP6 antibody titers. However, rP6 was less immunogenic than P6 when administered either without adjuvant or in alum and when tested in competitive inhibition studies with anti-P6 antibodies, was a less effective inhibitor than native P6, suggesting a diminution in some of the antigenic activity of rP6. In spite of these differences, rP6 was capable of eliciting a protective antibody response against live H. influenzae type b challenge in a modified infant rat model of bacteremia. These findings demonstrate that the non-fatty acylated rP6 could possibily be substituted for native P6 in a vaccine against H. influenzae.

N-methyl-D-aspartate receptor antagonists potentiate morphine's antinociceptive effect in the rat.

The interaction between morphine and three antagonists of the N-methyl-D-aspartate (NMDA) receptor. MK-801 (non-competitive channel blocker), dextromethorphan (clinically available non-competitive antagonist) and CGS19755 (competitive receptor antagonist), was examined in rats with the hot plate test. The NMDA antagonists were administered intraperitoneally and none of them caused antinociception at doses that did not produce motor deficits (0.1 mg kg-1 MK-801, 30 mg kg-1 dextromethorphan and 5 mg kg-1 CGS19755). However, pretreatment with the NMDA antagonists at these doses 30 min prior to subcutaneous injection of 5 mg kg-1 morphine significantly potentiated the antinociceptive effect of morphine, with strongest effect observed with dextromethorphan. It is suggested that blockade of NMDA receptors enhances the antinociceptive effect of morphine and NMDA antagonists may improve the analgesic efficacy of morphine in the clinic.

Alterations in somite patterning of Myf-5-deficient mice: a possible role for FGF-4 and FGF-6.

Mice carrying a targeted mutation in the gene for the myogenic factor Myf-5 fail to form major parts of the ribs, which leads to an unstable thorax and perinatal death. Here, we report that somites of Myf-5-deficient mice lack the expression of FGF-4 and FGF-6 while TGF beta-2 is expressed normally. Early sclerotomal markers, such as Pax-1 reveal no substantial reduction of sclerotome size. At E11.5 the condensing mesenchyme of the rib anlagen is considerably reduced in size in Myf-5 mutant mice. This may be caused by the lack of Myf-5-positive, FGF-expressing cells which normally are in close contact with the lateral sclerotome generating the rib progenitors. The potential role of FGFs and TGF beta on sclerotome formation is demonstrated in micromass cultures of early somites. Combinations of FGF-4 or FGF-6 with TGF beta-2 potentiate chondrogenesis suggesting that these growth factors emanating from early myotomal and dermomyotomal cells may have instructive or permissive effects on differentiation or outgrowth of sclerotomal cells.

Identification of a hemolytic activity elaborated by Haemophilus ducreyi.

Haemophilus ducreyi is the causative agent of the sexually transmitted disease chancroid. We have identified a hemolytic activity expressed by H. ducreyi. This activity is most readily detected when horse erythrocytes are used as a target; however, low levels of activity can be detected with sheep, human, or rabbit erythrocyte targets. The activity is heat labile and protease sensitive.