Cloning, functional activities and in vivo tissue distribution of rat NKR-P1+ TCR alpha beta + cells

We have successfully cloned nine NKR-P1+ TCR alpha beta + cells from PVG rat spleens, utilizing murine macrophage inflammatory protein-1 alpha (MIP-1 alpha) and IL-2. These clones are either double negative (DN, CD4-CD8-), which included clones 3.31, 3.71, 4.19, 4.59 and 4.65, or single positive (SP, CD4+CD8-), which included clones 1.64, 3.8, 3.76 and 3.78. No CD8+ clone was recovered. All nine clones are restricted in terms of their expression of the V beta antigens, since they express V beta 8.2 but not V beta 8.5, V beta 10 or V beta 16. These clones are agranular and they fall to generate NK or LAK activity upon incubation with IL-2, IL-12 or their combination. On the basis of their production of intracellular cytokines they can be divided into three categories: (I) SP clones (1.64, 3.8, 3.76 and 3.78) do not produce IL-2 or IL-4, but produce IFN-gamma and IL-12, and they vary in their production of IL-1, RANTES or tumor necrosis factor (TNF)-alpha; (II) DN clones 4.59 and 4.65 produce IL-1 alpha and IFN-gamma only, and fall to produce other cytokines; and (III) DN clones 3.31, 3.71 and 4.19 produce IL-1 alpha, IL-1 beta, IL-2, IL-12, IFN-gamma, RANTES and TNF-alpha. From all the clones examined only DN clones 3.31 and to a lesser degree 4.19 produce IL-4. In vivo tissue localization of clones 3.8, 3.31 and 4.59 shows that these cells distribute into the liver and bone marrow 24 h post i.v. administration. Their accumulation in the liver and bone marrow along with their ability to secrete various cytokines suggest that these cells may influence the generation, differentiation or apoptosis of immune or hematopoietic cells.      

Immunological and Antiviral Responses After Therapeutic DNA Immunization in Chronic Hepatitis B Patients Efficiently Treated by Analogues

A substudy of a phase I/II, prospective, multicenter clinical trial was carried out to investigate the potential benefit of therapeutic vaccination on hepatitis B e antigen-negative patients with chronic hepatitis B (CHB), treated efficiently with analogues. Patients were randomized in 2 arms, one receiving a hepatitis B virus (HBV) envelope DNA vaccine, and one without vaccination. At baseline, HBV-specific interferon (IFN)-γ–producing T cells were detected in both groups after in vitro expansion of peripheral blood mononuclear cells. Vaccine-specific responses remained stable in the vaccine group, whereas in the control group the percentage of patients with HBV-specific IFN-γ–producing T cells decreased over time. The vaccine-specific cytokine-producing T cells were mostly polyfunctional CD4⁺ T cells, and the proportion of triple cytokine-producer T cells was boosted after DNA injections. However, these T-cell responses did not impact on HBV reactivation after stopping analogue treatment. Importantly, before cessation of treatment serum hepatitis B surface antigen (HBsAg) titers were significantly associated with DNA or HBsAg clearance. Therapeutic vaccination in CHB patients with persistent suppression of HBV replication led to the persistence of T-cell responses, but further improvements should be searched for to control infection after treatment discontinuation.     

Kaposi's sarcoma complicating corticosteroid therapy for temporal arteritis

Combination immunosuppressive therapy, particularly in renal transplant recipients, is associated with a higher than expected risk of development of Kaposi's sarcoma. In this report, cutaneous dissemination of Kaposi's sarcoma occurred in a patient with temporal arteritis who was treated with corticosteroids. Reduction of the steroid dosage was followed by regression of the tumor. This sequence of events suggests a causal relationship between the evolution of the sarcoma and corticosteroid therapy. Although Kaposi's sarcoma may complicate corticosteroid therapy alone, the incidence is considerably lower than in renal transplant recipients receiving combination immunosuppressive therapy. Considering the large number of patients with temporal arteritis who are treated with steroids and that this is the first report of its association with Kaposi's sarcoma, it seems that other factors, perhaps genetic, might be important in the development of this neoplasm.     

Transfemoral Transcatheter Tricuspid Valve Replacement With the EVOQUE System: A Multicenter,Observational, First-in-Human Experience

ObjectivesThe purpose of this observational first-in-human experience was to investigate the feasibility and safety of the EVOQUE tricuspid valve replacement system and its impact on short-term clinical outcomes.BackgroundTranscatheter tricuspid intervention is a promising option for selected patients with severe tricuspid regurgitation (TR). Although transcatheter leaflet repair is an option for some, transcatheter tricuspid valve replacement (TTVR) may be applicable to a broader population.MethodsTwenty-five patients with severe TR underwent EVOQUE TTVR in a compassionate-use experience. The primary outcome was technical success, with NYHA (NYHA) functional class, TR grade, and major adverse cardiac and cerebrovascular events assessed at 30-day follow-up.ResultsAll patients (mean age 76 ± 3 years, 88% women) were at high surgical risk (mean Society of Thoracic Surgeons risk score 9.1 ± 2.3%), with 96% in NYHA functional class III or IV. TR etiology was predominantly functional, with mean tricuspid annular diameter of 44.8 ± 7.8 mm and mean tricuspid annular plane systolic excursion of 16 ± 2 mm. Technical success was 92%, with no intraprocedural mortality or conversion to surgery. At 30-day follow-up, mortality was 0%, 76% of patients were in NYHA functional class I or II, and TR grade was ≤2+ in 96%. Major bleeding occurred in 3 patients (12%), 2 patients (8%) required pacemaker implantation, and 1 patient (4%) required dialysis.ConclusionsThis first-in-human experience evaluating EVOQUE TTVR demonstrated high technical success, acceptable safety, and significant clinical improvement. Larger prospective studies are needed to confirm durability and safety and the impact on long-term clinical outcomes.     

Apatite-associated arthropathy: a clinical study of 14 cases and of 2 patients with calcific bursitis

Fourteen cases of acute calcific periarthritis and 2 cases of acute calcific bursitis are described. All patients had radiologic periarticular calcific deposits. Synovial fluid was available from 8 patients. Hydroxyapatite crystals were positively identified in 1 by x-ray diffraction analysis and by scanning and transmission electron microscopy. Apatite-associated arthropathy likely represents a form of crystal-induced inflammation. Three articular syndromes can be recognized; acute calcific periarthritis, acute (calcific) arthritis and a subacute-to-chronic arthritis resembling osteoarthritis. To improve patient classification, diagnostic criteria are proposed.     

Computed tomography in the diagnosis of early ankylosing spondylitis

Computed tomography (CT) was compared with plain radiography and quantitative sacroiliac (SI) scintigraphy in 28 patients with early ankylosing spondylitis (AS) of less than or equal to 10 years duration. Compared with conventional radiography, CT improved delineation of the SI joints and revealed more abnormalities and higher grades of sacroiliitis; this was significant in patients with early AS of less than or equal to 3 years duration. Quantitative sacroiliac scintigraphy showed higher SI joint: sacrum ratios of radioisotope uptake in patients with AS compared with controls. However, its diagnostic usefulness was limited by the frequency of inconsistent results and the lack of specificity. CT examination of the SI joints may be a useful adjunct in the diagnosis of early AS.     

Urethro-vesical function during spinal shock

Summary Twenty spinal shock patients were investigated with simultaneous urethrovesical, anal and rectal pressure recordings and EMG of the external urethral and anal sphincters. Dynamic and static urethral pressure profiles (UPP) were carried out with empty and full bladder. Baldder filling was accompanied by an increased resistance in the internal sphincter zone, which in turn was paralleled in the majority of cases by an elevation of pressure in the membranous urethra without concomitant increase of its EMG activity. This is suggestive of an increased sympathetic activity in the bladder neck area and in the smooth muscle component of the external urethral sphincter. Dynamic pullthrough UPP's displayed higher resistances in the membranous urethra than static interrupted UPP's pointing to the role played by the urethral muscosal receptors in eliciting artefactual results. Higher pressures were recorded in the juxtabulbar portion of the membranous urethra than in its mid portion pointing to a gradient of pressure within the external urethral sphincter itself. The amount of EMG activity recorded in the anal and urethral sphincters at rest was somewhat decreased; high pressures and distinct reflex activity were recorded in both sphincters showing that they escape spinal shock characterized primarily by areflexia. After defining spinal shock a rational explanation based upon neuroanatomical and neurophysiological findings is offered as to why somatic activity of the sacral segments escapes it as evidenced by clincial, urodynamic, and electromyographic recordings.