Thyroid microsomal/thyroid peroxidase autoantibodies show discrete patterns of cross-reactivity to myeloperoxidase, lactoperoxidase and horseradish peroxidase.

The recent cloning of the thyroid peroxidase (TPO) has shown that it is identical to the thyroid microsomal antigen (TMA), a potent antigen involved in autoimmune thyroid disease (ATD), which shares significant sequence homology with myeloperoxidase. The present study shows that autoantibodies (aAb) to the TMA/TPO antigen cross-react with human leucocyte myeloperoxidase, bovine lactoperoxidase and horseradish peroxidase. Cross-reactivity to myeloperoxidase was only apparent by ELISA using reduced and alkylated antigen preparations or by immunoblotting following denaturation with SDS. Sequential absorption of sera on SDS-denatured thyroid microsomes immobilized on Sepharose-4B followed by absorption on native microsomes removed all aAb specificities to TMA/TPO and the three peroxidase preparations, giving compelling evidence on the genuine cross-reactive nature of these aAbs. Sera from different patients contain different qualitative and quantitative specificities of aAb to the TMA/TPO antigen, confirming the polyclonal nature of this autoimmune response.     

Heat shock protein 70 (HSP70) and complement C4 genotypes in patients with hyperthyroid Graves'' disease.

The genetic polymorphisms of the heat shock protein 70 (HSP70) and complement component C4 were investigated in 90 patients with hyperthyroid Graves' disease and 92 normal control subjects. The 8.5-kb PstI HSP70 allele was strongly associated with Graves' disease when compared with controls (P less than 0.001). The presence of the 8.5-kb PstI HSP70 allele was strongly associated with a deletion of the C4A gene in both patients and controls (P less than 0.0003 and P less than 0.00005 respectively). However, in the absence of C4A gene deletion, the frequency of the 8.5-kb PstI HSP70 allele was still significantly higher in patients when compared with controls (P less than 0.04). These results suggest that the HSP70 locus may have an immunological role to play in autoimmune hyperthyroid Graves' disease.     

Surgical pathology of pulmonary thromboendarterectomy: a study of 54 cases from 1990 to 2001

Thromboendarterectomy is performed to treat chronic thromboembolic pulmonary hypertension with obstruction of main, lobar, or segmental pulmonary arteries. The present study evaluated surgical specimens removed between 1990 and 2001. Medical histories and microscopic slides were reviewed in each case. Study slides were stained with hematoxylin and eosin and Verhoeff-van Gieson and evaluated for thrombus, collagen, elastin, atherosclerosis, hemosiderin, calcification, and inflammation. The study group comprised 54 patients (30 women and 24 men), ranging in age from 33 to 77 years (mean, 58 years). Clinically, 28 (52%) had a history of deep leg vein thrombosis and 42 (78%) had a history of pulmonary embolism; 24 (44%) had both events. Coagulation abnormalities were documented in 15 (28%); autoimmune or hematologic disorders, in 8 (15%). Pulmonary thromboendarterectomy was bilateral in 52 patients (96%) and right-sided in 2. Six patients also had obstructions resected from the main pulmonary arteries. Obstruction limited to segmental arteries occurred only in women. Grossly, right-sided specimens were larger than left-sided ones (P = 0.003). Microscopically, ages of thrombi were uniform in 72% and variable in 28%. Intima was thickened in all patients and consisted of collagen (100%), elastin (67%), hemosiderin (56%), inflammation (53%), atherosclerosis (32%), and calcification (15%). We determined that pulmonary thromboendarterectomy was performed most often in middle-aged and elderly patients with a history of deep venous thrombosis or pulmonary embolism. Less than 50% of the patients had an identifiable coagulation, autoimmune, or hematologic abnormality. Most patients had bilateral disease and resections. Right-sided specimens were significantly larger than left-sided specimens, and lower lobe involvement was more common than involvement elsewhere. Resected tissues most commonly exhibited old organized thrombus.     

Surfactant protein D enhances phagocytosis and killing of unencapsulated phase variants of Klebsiella pneumoniae

Pulmonary surfactant protein D (SP-D) is a collagenous C-type lectin (collectin) that is secreted into the alveoli and distal airways of the lung. We have studied the interactions of SP-D and alveolar macrophages with Klebsiella pneumoniae, a common cause of nosocomial pneumonia. SP-D does not agglutinate encapsulated K. pneumoniae but selectively agglutinates spontaneous, unencapsulated phase variants, such as Klebsiella strain K50-3OF, through interactions with their lipopolysaccharides (LPS). These effects are calcium dependent and inhibited with maltose but not lactose, consistent with involvement of the SP-D carbohydrate recognition domain. Precoating of K50-3OF with SP-D enhances the phagocytosis and killing of these organisms by rat alveolar macrophages in cell culture and stimulates the production of nitric oxide by the NR-8383 rat alveolar macrophage cell line. SP-D similarly enhances the NO response to K50-3OF LPS adsorbed to Latex beads under conditions where soluble LPS or SP-D, or soluble complexes of SP-D and LPS, do not stimulate NO production. Our studies demonstrate that interactions of SP-D with exposed arrays of Klebsiella LPS on a particulate surface can enhance the host defense activities of alveolar macrophages and suggest that activation of macrophages by SP-D requires binding to microorganisms or other particulate ligands. Because unencapsulated phase variants are likely to be responsible for the initial stages of tissue invasion and infection, we speculate that SP-D-mediated agglutination and/or opsonization of K. pneumoniae is an important defense mechanism for this respiratory pathogen in otherwise healthy individuals.     

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.     

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.     

Effect of lithium carbonate therapy on thyroid immune status in manic depressive patients: a prospective study

Serum thyroid autoantibodies to thyroglobulin (TG) and thyroid microsomes (M) were measured by ELISA prospectively in 37 manic depressive patients prior to receiving lithium carbonate and during therapy with this drug for a mean of 16.2 months. They were also measured once in 27 normal subjects and several times in five psychiatric patients not receiving lithium. Sixteen patients (43%) had either thyroglobulin, microsomal antibodies or both before receiving lithium therapy. During therapy significant fluctuations in antibody titre, both upwards and downwards were observed in ten out of 12 patients with M antibodies and in nine out of 11 with TG antibodies. The fluctuations in antibody titre are consistent with an immunomodulatory effect of lithium as has been shown in animal studies. It is suggested that psychiatric patients should have thyroid antibodies measured routinely before and during lithium therapy.