IL-4- and IL-5-secreting lymphocyte populations are preferentially stimulated by parasite-derived antigens in human tissue invasive nematode infections

Helminth infections in humans and animals are associated with strong T helper 2 (Th2) responses. To determine whether parasite-derived Ag preferentially expand a Th2-like cell population, a filter immunoplaque assay was used to enumerate the frequencies (F0) of PBMC and CD4(+)-enriched PBMC from individuals with helminth infections secreting selected cytokines in response to parasite-derived (PAg) and nonparasite antigens (NPAg). In 20 individuals with lymphatic filariasis, frequency analysis of PBMC secreting IL-4 and IFN-gamma indicated that the F0 of PAg-specific IL-4-secreting cells (geometric mean F0 (GM): 1/12,100) was 57-fold higher than the corresponding F0 of NPAg-reactive cells (GM: 1/692,000; p < 0.02). In marked contrast, the F0 of IFN-gamma-secreting cells responding to PAg (GM: 1/2,700) did not differ from those of cells specific for NAPg (GM: 1/3,400; p = 0.83). In another group of helminth-infected individuals, the F0 of highly enriched CD4+ cells secreting IL-4 and IL-5 in response to PAg (GMs: 1/2,600 and 1/5,600 CD4+ cells, respectively) were also found to be significantly higher than those specific for NPAg (GMs: 1/291,000 and 1/303,000 CD4+; p < 0.05 and p < 0.01, respectively), whereas the corresponding F0 of IFN-gamma- and granulocyte-macrophage-CSF-secreting cells were equivalent for PAg and NPag. Furthermore, the proportion of PAg-specific IL-4- and IL-5-secreting CD4+ cells relative to all cells secreting the given cytokine were approximately 29-fold higher than the proportion of NPAg-specific cells secreting these cytokines. Again, the corresponding proportions of Ag-specific IFN-gamma-and GM-CSF-secreting CD4+ cells were equivalent for PAg and NPAg. Thus, in this ex vivo system, a circulating population of IL-4- and IL-5-secreting (Th2-like) cells has been shown to exist in humans; PAg appears to expand these cells preferentially.     

Abnormal behavioral responses to fenfluramine in patients with affective and personality disorders. Correlation with increased serotonergic responsivity

Serotonergic responsivity was assessed in 20 psychiatric patients by the prolactin response to a fenfluramine challenge test. During the fenfluramine challenge 6 of 20 patients (30%) spontaneously reported psychopathologic reactions that included: increased anxiety/agitation, psychotic symptoms, illusions, mood elevation, and anergia. The time of peak behavioral symptoms (2.5 +/- 0.8 hrs) corresponded closely to the time of peak increase in prolactin levels (3.0 +/- 1.1 hr). Abnormal behavioral responders had statistically significant greater increases in prolactin 1 to 4 hr after fenfluramine when compared to normal responders. Patients who developed an abnormal psychopathologic response to fenfluramine were characterized by higher levels of anxiety and agitation at the time of admission to the hospital but otherwise were not distinguishable on the basis of severity of other psychiatric symptoms. This study suggests that increased serotonergic transmission may trigger anxiety, psychosis, and mood elevation in specific vulnerable individuals, whereas other patients with similar psychiatric illnesses are not affected.     

Selective activation by bryostatin-1 demonstrates unique roles for PKC epsilon in neurite extension and tau phosphorylation

The purpose of this study was to contrast the discharge patterns of the same motor units during movements and during isometric contractions that were produced with comparable torque-time characteristics. Subjects performed elbow flexion and extension movements with predetermined acceleration characteristics. The average acceleration and deceleration profiles for the movements were reproduced in the isometric setting by presenting the kinematic profiles as templates for torque production. Trained subjects were able to match the first agonist (AG1) and antagonist (ANT) electromyographic (EMG) bursts, but tended to produce a smaller second agonist burst (AG2) in the isometric contraction. Twenty-five motor units from triceps brachii were studied. The same motor units (with one exception) were recruited and subsequently discharged in a similar fashion in both the isometric and movement tasks in the AG1 and ANT EMG bursts, with fewer motor unit discharges in the AG2 burst in the isometric contraction. The central control mechanisms appear to be the same for the acceleration phase of movement and isometric contraction, but differ during the deceleration phase.     

Exclusion of BMP6 as a candidate gene for cleidocranial dysplasia

Cleidocranial dysplasia (CCD) is an autosomal dominant, generalized skeletal dysplasia in humans that has been mapped to the short arm of chromosome 6. We report linkage of a CCD mutation to 6p21 in a large family and exclude the bone morphogenetic protein 6 gene (BMP6) as a candidate for the disease by cytogenetic localization and genetic recombination. CCD was linked with a maximal two-point LOD score of 7.22 with marker D6S452 at theta = 0. One relative with a recombination between D6S451 and D6S459 and another individual with a recombination between D6S465 and CCD places the mutation within a 7 cM region between D6S451 and D6S465 at 6p21. A phage P1 genomic clone spanning most of the BMP6 gene hybridized to chromosome 6 in band region p23-p24 using FISH analysis, placing this gene cytogenetically more distal than the region of linkage for CCD. We derived a new polymorphic marker from this same P1 clone and found recombinations between the marker and CCD in this family. The results confirm the map position of CCD on 6p21, further refine the CCD genetic interval by identifying a recombination between D6S451 and D6S459, and exclude BMP6 as a candidate gene.     

The posterior operative approach for cervical radiculopathy

Cervical disc disease includes acute herniation and chronic disc degeneration with secondary changes in the associated bone. The latter may lead to the spectrum of cervical spondylitic stenosis, which is considered to be multilevel and may be more of a bony disease. Clinically, cervical disc disorders can be divided into several disorders. The disorder of true cervical radiculopathy is associated with lateral compression of the nerve root. When this condition is due to a lateral soft disc herniation or lateral bony stenosis, the posterior cervical laminoforaminotomy is commonly used. It is a procedure that works extremely well in the vast majority of patients and there is no risk of spinal instability; therefore, no fusion is required. The details of operative care have been described. In patients who have persistent radicular problems after a failed anterior cervical interspace procedure, the posterior cervical laminoforaminotomy with posterior wiring and fusion is a simple and effective operative option.     

Expert statement and assessment of medical impairment in work-related pulmonary disease

The Norwegian Societies of Thoracic Medicine and Occupational Medicine established a working group to standardise diagnostic procedures and evaluation of work-related respiratory disorders. In cases of suspected work-related diseases the physician may be asked by the National Insurance Administration or an insurance company to make a statement which will be one of the documents used to decide the patient's right to compensation benefit. We discuss the role of the physician as an independent expert. This is different from his role as clinician. The statement should include a balanced presentation of information from different sources, including health and occupational history, and the employer's information about the work environment (quantitative and qualitative exposure data). The statement must also include the results of a clinical examination and an assessment of functional status based on objective tests. The paper contains recommendations for evaluation of permanent impairment in light of the present Norwegian laws and regulations.     

A simple approach to intracytoplasmic sperm injection

OBJECTIVE: To describe a simple injection apparatus and method for performing intracytoplasmic sperm injection in a clinical IVF program. DESIGN: A prospective clinical trial of intracytoplasmic sperm injection. SETTING: A private office-based fertility program. PATIENTS: Five couples undergoing IVF-ET with intracytoplasmic sperm injection as a treatment for male factor infertility. INTERVENTIONS: Intracytoplasmic sperm injection was performed at room temperature (23.5 to 24.5 degrees C) in a simple zwitterion-buffered medium. MAIN OUTCOME MEASURES: Fertilization rates, cleavage rates, clinical pregnancy rates, implantation rates. RESULTS: Intracytoplasmic sperm injection was performed on 44 fresh oocytes from five patients. Twenty-three oocytes fertilized (52.3%) and 22 zygotes cleaved (95.7%). Three of five patients became pregnant (60%), resulting in the live birth of one normal male infant, one continuing singleton pregnancy, and one continuing twin gestation (46XX, 46XY). The implantation rate was 23.5%. CONCLUSION: Intracytoplasmic sperm injection can be performed successfully in a simple medium at room temperature using commercially available microtools.     

Hyaluronic acid induced hyaluronic acid binding protein phosphorylation and inositol triphosphate formation in lymphocytes

In this report, the role of 34 kDa HA-binding protein in hyaluronic acid-induced cellular signalling in lymphocytes has been examined. The binding of 125I-HA to lymphocytes in vivo was found to be inhibited by pre-incubation of the cells with anti-34 kDa HA-binding protein antibodies, thus confirming 34 kDa HA-binding protein as the specific HA-receptor in lymphocytes. This observation was substantiated by anti-34 kDa HA-binding protein antibodies immunoblotting and 125I-HA ligand blotting of lymphocytes cell lysate. The HA-induced cell aggregation, tyrosine phosphorylation and cytoskeletal protein phosphorylation demonstrate the HA-induced early cellular signalling events in lymphocytes. Further, to study the involvement of 34 kDa HA-binding protein in mitogen induced lymphocyte signalling, we studied in vivo phosphorylation and secondary messenger formation. The enhanced 34 kDa HA-binding protein phosphorylation by HA and the inhibition of cellular aggregation and IP3 formation by anti-HA-binding protein antibodies revealed that 34 kDa HA-binding protein is one of the potential mediators in HA-induced signal transduction.     

A PET study of the neural systems of stuttering

The cause of stuttering is unknown. Failure to develop left-hemispheric dominance for speech is a long-standing theory although others implicated the motor system more broadly, often postulating hyperactivity of the right (language nondominant) cerebral hemisphere. As knowledge of motor circuitry has advanced, theories of stuttering have become more anatomically specific, postulating hyperactivity of premotor cortex, either directly or through connectivity with the thalamus and basal ganglia. Alternative theories target the auditory and speech production systems. By contrasting stuttering with fluent speech using positron emission tomography combined with chorus reading to induce fluency, we found support for each of these hypotheses. Stuttering induced widespread overactivations of the motor system in both cerebrum and cerebellum, with right cerebral dominance. Stuttered reading lacked left-lateralized activations of the auditory system, which are thought to support the self-monitoring of speech, and selectively deactivated a frontal-temporal system implicated in speech production. Induced fluency decreased or eliminated the overactivity in most motor areas, and largely reversed the auditory-system underactivations and the deactivation of the speech production system. Thus stuttering is a disorder affecting the multiple neural systems used for speaking.