Treatment for “Helpless” Women Suffering from Chronic Spinal Pain: A Randomized Controlled 18-Month Follow-Up Study

This prospective randomized controlled outcome study was designed to evaluate whether a MultiModal Cognitive—Behavioral Treatment for chronic spinal pain (MMCBT) specifically designed for women has an increased effect on well being and return to work compared to a regular MMCBT regimen. In Sweden, spinal pain is most prevalent among women. A tremendous amount of money is spent on secondary prevention of spinal pain. Yet, little is known about the effect of the interventions. A need for well designed outcome studies exist. Fifty-four subjects from a cohort of all registered sick-listed women in three districts of Stockholm participated in the study. Subjects were allocated by central randomization into two groups. One group was treated with a regular MMCBT program and the other group with a MMCBT program specifically designed for women. Assessments were performed at pretreatment–posttreatment (last treatment day) and at 6 and 18 months posttreatment. Questionnaires covering the bio-psycho-social spectra of the chronic pain syndrome, and sick leave were used to measure outcome. Intention to treat and true to protocol analyses were performed. The only significant differences found between groups were improvements in self-reported disability and in coping with pain, favoring the experimental treatment. About one-third of the variance in disability was explained by the set of pain-coping strategies assessed in the study. The results do not lend sufficient statistical support to warrant acceptance of the experimental treatment as superior to the regular treatment in improving health and sick leave. Further investigation with larger groups is needed before a solid scientific conclusion can be drawn.     

Haemophilus influenzae causing conjunctivitis in day-care children

The role of Haemophilus influenzae in acute purulent conjunctivitis was studied during an outbreak among children in day care. Five day-care centers contributed 20 cases and 35 controls. All the children were subjected to culture of the nasopharynx and the eyes. H. influenzae was carried in the nasopharynx of 53% of the children (range between day care centers, 20 to 91%). Of the 20 children with acute conjunctivitis 8 had eye cultures positive for H. influenzae, 2 had Moraxella and the remaining were culture-negative. Ten colonies of H. influenzae were isolated from each positive culture and identified by capsular type, biotype and multi-locus enzyme electrophoresis. All but one of the isolates were nonencapsulated. They belonged to 4 biotypes and 8 electrophoretic types. The same strain was recovered from the eyes and nasopharynx of the symptomatic children, suggesting that the H. influenzae in the eyes originated from the nasopharynx. There was no evidence for spread of the same H. influenzae strains between day-care centers. Even within each center the Haemophilus strains recovered from the eyes varied among the symptomatic children. The in vitro capacity to attach to oropharyngeal epithelial cells was not increased among the H. influenzae recovered from the eyes. The results question if the majority of conjunctivitis cases were caused by H. influenzae and suggested that eyes were colonized with the nasopharyngeal carrier strain rather than infected by an isolate with special virulence for the eye.     

Effects of IFN-gamma and interleukin-1beta on major histocompatibility complex antigen and intercellular adhesion molecule-1 expression by 9L gliosarcoma: relevance to its cytolysis by alloreactive cytotoxic T lymphocytes.

To enhance the efficacy of cellular immunotherapy for gliomas, we tested the concept of using proinflammatory cytokine treatment with interferon-gamma (IFN-gamma) or interleukin-1beta (IL-1beta) or both to render glioma cells more susceptible to cytolysis by alloreactive cytotoxic T lymphocytes (aCTL). The cytokines, separately or in combination, were able to upregulate major histocompatibility complex (MHC) class I antigen or intercellular adhesion molecule-1 (ICAM-1) on Fischer rat 9L gliosarcoma cells. 9L cells were incubated in vitro for 24, 48, or 72 h with varying concentrations of rat IFN-gamma (0-2000 U/ml) or recombinant human IL-1 (rHUIL-1) (0-1000 U/ml) or both. By 48 h, IFN-gamma (500 U/ml) maximally induced the percentage of positive expressing cells and the relative antigen density of MHC class I and ICAM-1 on 9L cells, whereas IL-1 induced only ICAM-1 expression. Simultaneous incubation of IL-1 with IFN-gamma did not further affect the induction of class I on 9L cells more than that achieved with IFN-gamma alone. 9L cells with upregulated MHC class I and ICAM-1 expression were more sensitive to lysis by aCTL in in vitro cytotoxicity assays, regardless of whether the precursor aCTL came from naive or from 9L-immunized rats. Furthermore, inhibition of 9L cytotoxicity in assays that included blocking antibodies to MHC class I or to ICAM-1 revealed that T cell receptor (TCR) interactions with MHC class I and that ICAM-1 interactions with lymphocyte function-associated-1 (LFA-1) antigen account for a portion of the glioma lysis by aCTL.     

Sleep and its homeostatic regulation in mice lacking the adenosine A1 receptor

Sleep deprivation (SD) increases extracellular adenosine levels in the basal forebrain, and pharmacological manipulations that increase extracellular adenosine in the same area promote sleep. As pharmacological evidence indicates that the effect is mediated through adenosine A1 receptors (A1R), we expected A1R knockout (KO) mice to have reduced rebound sleep after SD. Male homozygous A1R KO mice, wild-type (WT) mice, and heterozygotes (HET) from a mixed 129/C57BL background were implanted during anesthesia with electrodes for electroencephalography (EEG) and electromyography (EMG). After 1 week of recovery, they were allowed to adapt to recording leads for 2 weeks. EEG and EMG were recorded continuously. All genotypes had a pronounced diurnal sleep/wake rhythm after 2 weeks of adaptation. We then analyzed 24 h of baseline recording, 6 h of SD starting at light onset, and 42 h of recovery recording. Neither rapid eye movement sleep (REM sleep) nor non-REM sleep (NREMS) amounts differed significantly between the groups. SD for 6 h induced a strong NREMS rebound in all three groups. NREMS time and accumulated EEG delta power were equal in WT, HET and KO. Systemic administration of the selective A1R antagonist 8-cyclopentyltheophylline (8-CPT) inhibited sleep for 30 min in WT, whereas saline and 8-CPT both inhibited sleep in KO. We conclude that constitutional lack of adenosine A1R does not prevent the homeostatic regulation of sleep.     

Characterization of an IgA receptor from group B streptococci: specificity for serum IgA

Some strains of group B streptococci express a cell surface protein which binds IgA. This report describes some properties of such an IgA receptor and compares it with a previously described IgA receptor from group A streptococci. The group B receptor was released in an almost pure form from bacteria incubated at elevated pH, and could be isolated by IgA-Sepharose affinity chromatography. The sequence of the N-terminal 19 amino acid residues was unique. The receptor preferentially binds IgA of human origin, as shown in immunoblotting experiments with purified IgA from nine different species. The affinity constant of the purified receptor for serum IgA was determined to be 3.5 x 10(8) M-1, but for secretory IgA it was too low to allow determination. This result indicates that secretory component and/or J chain interferes with the binding of IgA to this type of bacterial receptor, which may be one of the physiological functions of these polypeptides. A reduction in affinity was also observed for another complexed form of IgA, alpha 1-microglobulin-IgA. The group B receptor is antigenically unrelated to the IgA receptor from group A streptococci (protein Arp), but competitive inhibition experiments indicate that they bind to the same region in IgA. The implications of these findings, and the biological role of bacterial IgA receptors, are discussed.     

Characterization of FMR1 proteins isolated from different tissues

FMR1 protein expression was studied in different tissues. Inhuman, monkey and murine tissues, high molecular mass FMR1 proteins(67–80 kDa) are found, as shown in lymphobiastoid celiiines. The identity of these proteins was confirmed by theirabsence in tissues from patients with the fragile X syndromeand a FMR1 knock-out mouse. An IIe367Asn substitution in theFMR1 protein did not aiter the transiation, processing and localizationof FMR1 proteins in lymphoblastoid cells from a patient carryingthis mutation. All the high molecular mass FMR1 proteins isolatedfrom normal lymphoblastoid cells and cells from the patientwith the IIe367Asn substitution were able to bind RNA. However,the FMR1 proteins of the patient had reduced affinity for RNAbinding at high salt concentrations. In some human, monkey andmurine tissues low molecular mass FMR1 proteins (39–41kDa) were found, which had the same N terminus as the 67–90kDa isoforms, but differ in their C terminus and are thereforemost likely the result of carboxy-terminal proteolytic cleavage.These low molecular mass FMR1 proteins did not bind RNA, incontrast with the high molecular mass FMR1 proteins. The significanceof these low molecular mass proteins remains to be studied.     

Rapid fragmentation and reorganization of Golgi membranes during frustrated phagocytosis of immobile immune complexes by macrophages.

The authors have observed the rapid reorganization of the cellular membranes of macrophages during Fc receptor-mediated frustrated phagocytosis of immune complex-coated surfaces. As the macrophages spread, large, clear basal vacuoles and anastamosing tubules were formed, occasionally contiguous with the adherent surface. Coated vesicles also were observed. This process was accompanied by a rapid reorganization of the Golgi complex region of the macrophages, which was observed using trimetaphosphatase histochemistry and an antibody to a Golgi membrane antigen as markers. On contact of the macrophages with the immune complexes, the Golgi complexes, which were tightly clustered around the centrioles, dispersed into vesicles and reorganized near the basal surface. The Golgi cisternae swelled, fragmented, and decreased in number. Golgi membrane antigen was found in the large basal vacuoles and also associated with the adherent basal surface of the macrophages. This indicates that the Golgi complexes were reorganized, in part, by a direct recruitment of their membranes to the increasing basal surface area of the spreading macrophages. The changes in the structure of the Golgi complexes were reversible; by 2 hours, the complexes had recovered their normal organization, with an accompanying decrease in the number of large basal vacuoles. These data suggest that the dynamic interrelationship among the Golgi membranes, intracellular vacuoles, and the plasma membrane can be perturbed by membrane spreading on a nonphagocytosable surface.     

BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses

Exerting its actions pre-, post- and peri-synaptically, brain-derived neurotrophic factor (BDNF) is one of the most potent modulators of hippocampal synaptic function. Here, we examined the effects of BDNF on a rapidly recycling pool (RRP) of vesicles within excitatory synapses. First, we estimated vesicular release in hippocampal cultures by performing FM4-64 imaging in terminals impinging on enhanced green fluorescent protein (eGFP)-labelled dendritic spines – a hallmark of excitatory synapses. Consistent with a modulation of the RRP, BDNF increased the evoked destaining rate of FM4-64 only during the initial phase of field stimulation. Multiphoton microscopy in acute hippocampal slices confirmed these observations by selectively imaging the RRP, which was loaded with FM1-43 by hyperosmotic shock. Slices exposed to BDNF showed an increase in the evoked and spontaneous rates of FM1-43 destaining from terminals in CA1 stratum radiatum, mostly representing excitatory terminals of Schaffer collaterals. Variance-mean analysis of evoked EPSCs in CA1 pyramidal neurons further confirmed that release probability is increased in BDNF-treated slices, without changes in the number of independent release sites or average postsynaptic quantal amplitude. Because BDNF was absent during dye loading, imaging, destaining and whole-cell recordings, these results demonstrate that BDNF induces a long-lasting enhancement in the probability of transmitter release at hippocampal excitatory synapses by modulating the RRP. Since the endogenous BDNF scavenger TrkB-IgG prevented the enhancement of FM1-43 destaining rate caused by induction of long-term potentiation in acute hippocampal slices, the modulation of a rapidly recycling vesicle pool may underlie the role of BDNF in hippocampal long-term synaptic plasticity.     

Connective tissue repair in circumferential periodontal defects in dogs following use of a biodegradable membrane

A biodegradable polylactic acid membrane was evaluated for its ability to enhance periodontal regeneration. In 8 Labrador dogs, circumferential defects were created around the maxillary 1st premolars. The defects were combination "1-wall vertical and horizontal". A membrane was adjusted to cover the defect on one side of the jaw, while the contralateral tooth served as control without membrane. After 3 months, healing was evaluated histologically. The results demonstrated that the amount of connective tissue repair with newly formed cementum approximated 50% of the defect height for both test and control groups. Thus, no advantage to the use of membrane was found, which is contradictory to the findings of our previous dog study using the same biodegradable membrane. The possible reasons for this difference in results are discussed relative to suggested mechanisms for membrane effects in periodontal regeneration.