Chimaeric anti-CD4 monoclonal antibody cross-linked by monocyte Fcγ receptor mediates apoptosis of human CD4 lymphocytes

Previous studies have shown that murine anti-CD4 monoclonal antibody, cross-linked by rabbit anti-mouse immunoglobulin, could mediate apoptosis of murine CD4⁺ lymphocytes when they were stimulated by T cell receptor antibody. In this study, we have shown that the murine anti-CD4 monoclonal antibody, OKT4, can induce apoptosis in human CD4⁺ T cells stimulated by the recall antigen tuberculin purified protein derivative (PPD) only when cross-linked by rabbit anti-mouse immunoglobulin. The chimeric anti-CD4 monoclonal antibody, cM-T412 whose Fc fragment is human, was able to cause apoptosis without cross-linking by a second antibody. Similarly, abolition of PPD-induced proliferation of peripheral blood mononuclear cells by cM-T412 did not require cross-linking with rabbit anti-human immunoglobulin. Inhibition of proliferation by cM-T412 could be reduced by pre-treating monocytes with heat-aggregated human IgG. This suggested that monocyte Fcγ receptors might be cross-linking the human Fc of cM-T412. Propidium iodide staining together with immunofluorescence showed that the apoptotic cells were indeed CD4⁺ lymphocytes. It is proposed that during treatment with cM-T412 in autoimmune disease such as rheumatoid arthritis, cM-T412-coated CD4 T cells, when they are subsequently stimulated by the unknown arthritogenic antigen, may undergo apoptotic cell death through cross-linking of cM-T412 on Fey receptor-positive cells within the joint.     

Steroid hormone receptors in human salivary gland tumours.

Major salivary gland tumours were studied for the presence of hormone receptors for oestrogen and progesterone. Of the eight salivary gland tumours exhibiting varied histology, none showed high affinity receptors for oestrogen or progesterone. Salivary tissue from four patients with non-neoplastic salivary gland disease was also studied and found not to contain high affinity receptor sites. The absence of hormone receptors in these glands suggests that such tumours are not dependent on endocrine function.     

New families of adhesion molecules play a vital role in platelet functions

Adhesion molecules play a crucial part in cell-matrix and in cell-cell interactions. These interactions, which are essential to the body's defense processes, involve adhesion molecules belonging to different families: integrins, immunoglobulins and selectins. Integrins are expressed by a large number of tissues, whereas other adhesion molecule families are restricted to a small number of cell types. A recent symposium dealt with the recruitment of circulating platelets at specific sites, their adhesion to extracellular matrix components and their activation by agonists leading to aggregation or attachment to other cells. These events, supporting hemostasis and thrombosis, involve integrins, selectins and other adhesion molecules. This report focuses on newly reported integrins (GPIa, GPIc, GPIIa), selectins (GMP-140) and GPIIIb, previously known as 'minor' surface oriented platelet glycoproteins. Major membrane glycoproteins such as GPIIb-IIIa (an integrin) and GPIb, which also play a vital role in platelet functions, have been extensively reviewed elsewhere.     

The behaviour of strains of the virus of foot-and-mouth disease in pig,calf, ox and lamb kidney tissue cultures

Summary Strains of the virus of foot-and-mouth disease obtained from different hosts and tissue cultures were tested in tissue cultures of pig, calf, ox and lamb kidneys for their ability to multiply and produce cytopathogenic effects. It was found that whereas cattle and kidney strains of the virus multiplied well in the cultures with cytopathogenic effect, mouse and egg adapted strains did not multiply or show cytopathogenic effect to the same extent especially in the ox and calf kidneys, and this could be correlated with their behaviour in cattle, pigs and cattle tongue epithelium tissue cultures. With all the strains used it was found possible to produce plaques on pig kidney monolayers, but the size and shape of the plaque varied as well as the relation of plaque titre to the titre in mice. The plaque size and plaque population from different sources were compared, and it was found that the relative number of the different plaque sizes varied with the source of the virus and changed in passage in the different systems. The possible significance of these findings in relation to vaccine preparation and adaptation of the virus is discussed.Part of the work described represents the kidney tissue culture side of experiments on attenuated strains of the virus of foot-and-mouth disease. We are grateful to our colleagues at Pirbright for the supply of virus strains and the results of many cattle, egg and mouse titrations.We would also like to thank MissP. Tremayne-Smitli, Mr.W. Chapman and Mr.D. Maskell for their excellent assistance in this work.     

Interleukin 17 modulates the immune response to vaccinia virus infection

Interleukin 17 (IL-17) is a newly identified cytokine that has a homolog in herpesvirus saimiri. We inserted murine IL-17 into vaccinia virus to study the role of IL-17 in viral infection. Vaccinia virus expressing IL-17 (vv-IL17) and its parental control virus (vv-pRB) grew to similar titers in vitro; however, vv-IL17 was more virulent in mice with a threefold lower LD(50) than for vv-pRB, and mean time to death of 2.8 days versus 4.5 days. Mice infected with vv-IL17 had higher titers of virus in the ovaries (P < 0.02) and showed a decrease in NK cell cytotoxicity (P < 0.02) on day 3 after infection. No significant difference was found in CTL activity. In addition, a significant decrease in IgG2a (P < 0.01) and increases in IgG1, IgG3, and IgA (P < 0.03) vaccinia virus-specific antibody titers were observed in mice infected with vv-IL17 versus vv-pRB, suggesting a Th-2-like response to infection. These data indicate that IL-17 modulates the immune response during virus infection.     

Alcohol Assessment in Psychiatric Patients

Alcohol use disorders in persons with co-occurring psychiatric disorders are associated with high rates of psy-chosocial instability and poorer treatment outcomes. Thus, assessment of alcohol use and abuse should become an integral part of psychiatric care. Because setf-report-based measures are frequently used, issues of reliability and validity in this population should be critically examined. The purpose of this article is to review and critique the existing empirical literature that has evaluated the psychometric integrity of self- report-based measures in psychiatric settings, and to outline a research agenda that promises to enhance the accuracy of alcohol assessment by persons receiving psychiatric treatment.     

Strachey's Shadow: A Re-examination of the Use of the Mutative Interpretation

James Strachey published his seminal paper on the nature of therapeutic action in 1934 in which he introduced his ideas on the mutative interpretation. He saw interpretation as the cornerstone of the psychoanalytic method. Since then, there has been a great deal of work looking at the essential nature of the interpretation and how it can promote change. By the1960s, Loewald and others were discussing how interpretation needed to incorporate new psychoanalytic thinking, particularly in the area of object relations. As the intersubjectivity of the psychoanalytic encounter gained more prominence, the use of the structural interpretation decreased. The author suggests that there is still need for further work on how interpretation can promote change. Using theoretical ideas and clinical examples, the paper concludes that the mutative interpretation continues to offer something potentially transformative, but that the technique has to take account of relational aspects of the treatment and the developmental issues of the patient. However, the clinician's relationship with the ideas about a mutative interpretation can also affect the clinician's ability to use it to a therapeutic effect.     

p75(NTR) gene and suicide attempts in young adults with a history of childhood-onset mood disorder.

Recently, evidence has accumulated for the role of neurotrophic processes in mood disorders. Neurotrophins operate on receptors, one of which is the p75 neurotrophin receptor (p75(NTR)). We examined three p75(NTR) markers at the p75(NTR) gene, including a missense polymorphism that changes serine to leucine (S205L), for association with suicide attempt (SA) in 203 childhood-onset mood disorder (COMD) cases. There was no difference between COMD suicide attempters and COMD non-attempters with logistic regression models for any of the three markers. We also compared the three polymorphisms between 192 COMD cases and 192 matched healthy controls and found no significant differences between COMD and healthy controls. Our results do not support an association of the p75(NTR) S205L polymorphism with risk for COMD or SA in COMD.     

Effects of gold sodium thiomalate,cyclosporin A,cyclophosphamide, and placebo on collagen-induced arthritis in rats

The prophylactic and therapeutic effects of gold sodium thiomalate, cyclosporin A, cyclophosphamide, and placebo on collagen-induced arthritis (CIA) were evaluated in DA rats. Prophylactic treatment with cyclosporin A and cyclophosphamide suppressed the arthritis incidence, clinical inflammation, destructive bone changes, and development of anti-collagen antibody in DA rats subsequently injected with porcine type-II collagen. Therapeutic treatment with cyclosporin A and cyclophosphamide had a definite suppression on established CIA when started 21 days after the initial collagen injection, but the suppression was less marked than that of prophylactic treatment. Gold had no impact on CIA in DA rats when administered either prophylactically or therapeutically.     

Genetic linkage analysis identifies new proximal and distal flanking markers for the X-linked agammaglobulinemia gene locus, refining its localization in Xq22

Genetic linkage analysis has been instrumental in mapping thegene for X-linked agammaglobulinemia (XLA) to the proximal longarm of the human X chromosome, to Xq22. Due to the relativerarity of this disease the localization of the gene within Xq22has remained imprecise. We have investigated twenty-nine familiesaffected by XLA and have found no recombinants with the DXS178locus in over 30 informative meioses. DXS178 is now the mostreliable and informative locus for use in pre-natal diagnosisand carrier detection of XLA. In addition, we have identifiednew closely linked proximal and distal flanking markers forXLA, DXS442 and DXS101, respectively. These loci are separatedby 2cM, considerably reducing the extent of DNA within whichthe XLA locus can be contained. This will open up the way formore directed positional cloning efforts for the isolation ofthe XLA gene.