Differential coupling of CC chemokine receptors to multiple heterotrimeric G proteins in human interleukin-2-activated natural killer cells

Using two different approaches, we have investigated the types of G proteins coupled to CC chemokine receptors. First, permeabilization of interleukin-2-activated natural killer (IANK) cells with streptolysin-O and introduction of anti-G protein antibodies inside these cells resulted in the following. (1) Anti-G(s), anti-G(o), and anti-G(z) inhibited the migration of IANK cells in response to macrophage- inflammatory protein-1 alpha (MIP-1 alpha), monocyte chemoattractant protein-1 (MCP-1), or regulated on activation normal T cell expressed and secreted (RANTES). (2) Anti-Gi inhibited their migration in response to MCP-1 or RANTES but not in response to MIP-1 alpha. Second, incubation of IANK cell membranes with anti-G protein antibodies before incubating with (gamma-35S) GTP or (gamma-32P) GTP, resulted in the following. (1) Anti-G(s), anti-G(o), or anti-G(z) inhibited GTP binding and GTPase activity in the presence of MIP-1 alpha, or RANTES. (2) Anti- G(i) inhibited GTP binding and GTPase activity in the presence of MCP-1 or RANTES but not in the presence of MIP-1 alpha. The inhibitory effect of anti-G protein antibodies was reversed upon incubating these antibodies with their respective synthetic peptides before addition to IANK cell membranes. These results suggest that MCP-1 and RANTES receptors are promiscuously coupled to multiple G proteins in IANK cell membranes and that this coupling is different from MIP-1 alpha receptors, which seem to be coupled to G(s), G(o), and G(z) but not to G(i).     

Pre-B acute lymphoblastic leukemia cells may induce T-cell anergy to alloantigen

Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance.     

Cardiac autonomic blockade in sinus disease and indication for a pacemaker

Functional autonomic blockade (FAB) with metoprolol (0.2 mg/kg body weight) and atropine sulphate (0.04 mg/kg) was carried out in 23 patients, 20 to 81 years old (mean age 61 years) with symptomatic sick sinus syndrome with clinical indication for permanent pacing. Several measurements were determined before and after FAB, 7 had normal intrinsic heart rate (IHR) and 16 abnormal. With normal IHR, 3 had severe autonomic regulation disturbances and in only two patients the corrected sinus nodal recovery time (SNRTC) and the sinoatrial conduction time (SACT) were prolonged after FAB. On the 16 patients with abnormal IHR only 4 had severe extrinsic autonomic influence and 15 had SACT and SNRTC prolonged after FAB. All measurements were determined by standard electrocardiographic surface tracings. Indications for permanent pacing were reduced to intrinsic sick sinus syndrome and bradycardia with severe autonomic disturbances in symptomatic patients.     

IgG Against Dengue Virus in Healthy Blood Donors,Zanzibar, Tanzania

We conducted a seroprevalence survey among 500 healthy adult donors at Zanzibar National Blood Transfusion Services. Dengue virus IgG seroprevalence was 50.6% and independently associated with age and urban residence. These data will aid in building a surveillance, preparedness, and response plan for dengue virus infections in the Zanzibar Archipelago.Key words: dengue, seroprevalence, Zanzibar, viruses, vector-borne infections     

Biceps Detachment Decreases Joint Damage in a Rotator Cuff Tear Rat Model

Background

Pathology in the long head of the biceps tendon often occurs in patients with rotator cuff tears. Arthroscopic tenotomy is the most common treatment. However, the role of the long head of the biceps at the shoulder and the consequences of surgical detachment on the remaining shoulder structures remain unknown.

Questions/purposes

We hypothesized that detachment of the long head of the biceps, in the presence of supraspinatus and infraspinatus tears, would decrease shoulder function and decrease mechanical and histologic properties of both the subscapularis tendon and the glenoid articular cartilage.

Methods

We detached the supraspinatus and infraspinatus or the supraspinatus, infraspinatus, and long head of the biceps after 4 weeks of overuse in a rat model. Animals were gradually returned to overuse activity after detachment. At 8 weeks, the subscapularis and glenoid cartilage biomechanical and histologic properties were evaluated and compared.

Results

The group with the supraspinatus, infraspinatus, and long head of the biceps detached had greater medial force and decreased change in propulsion, braking, and vertical force. This group also had an increased upper and lower subscapularis modulus but without any differences in glenoid cartilage modulus. Finally, this group had a significantly lower cell density in both the upper and lower subscapularis tendons, although cartilage histology was not different.

Conclusions

Detachment of the long head of the biceps tendon in the presence of a posterior-superior cuff tear resulted in improved shoulder function and less joint damage in this animal model.

Clinical Relevance

This study provides evidence in an animal model that supports the use of tenotomy for the management of long head of the biceps pathology in the presence of a two-tendon cuff tear. However, long-term clinical trials are required.