Oligoclonal populations of T and B cells in a case of angioimmunoblastic T-cell lymphoma predominantly infiltrated by T cells of the VB5.1 family.

AIMS: Immunohistological and molecular characterisation of a case of peripheral T-cell lymphoma (PTCL) of angioimmunoblastic T-cell lymphoma (AILD) type. METHODS: Frozen and paraffin wax sections of the diagnostic lymph node were stained with a panel of T- and B-cell lineage monoclonal antibodies. DNA was isolated from the paraffin wax embedded biopsy material for T-cell receptor (TCR) and immunoglobulin (Ig) PCR amplification, and resultant PCR products were cloned and sequenced. RESULTS: Immunohistological analysis of the presenting lymph node was consistent with an extensive infiltrate of pleomorphic CD3+CD8+ lymphocytes. Most (>80%) of these infiltrating CD3+ cells were also positive for the TCR VB5.1 gene family product, and were shown to be oligoclonal by TCRB PCR amplification and sequencing. Three oligoclones of B cells were also demonstrable by PCR amplification with Ig heavy chain primers and sequencing, a finding at variance with the diagnosis of AILD. CONCLUSIONS: These data demonstrate the complexity and heterogeneity of PTCL which require extensive histological examination and molecular characterisation.     

Familial hemiplegic migraine and autosomal dominant arteriopathy with leukoencephalopathy (CADASIL)

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described familial cerebrovascular disorder shown to map to chromosome 19q12. Familial hemiplegic migraine has also been shown in some families to map close to the CADASIL locus. The fully developed CADASIL phenotype consists of recurrent strokes developing in the fourth decade, progressing to a pseudobulbar palsy, spastic quadriparesis, and subcortical dementia. In an Irish family 15 members were fully investigated by magnetic resonance scanning; 10 had typical magnetic resonance features of CADASIL. Five members of this family had familial hemiplegic migraine and 4 of these had magnetic resonance evidence of CADASIL. Two other members had migraine with and without aura as a presenting clinical symptom of CADASIL. This disorder has been shown by linkage analysis to map to the CADASIL locus at chromosome 19. The phenotype at presentation of CADASIL in this family was variable and age related and included familial hemiplegic migraine, migraine with and without aura, transient ischemic attacks, strokes, and spinal cord infarction. This family study increases our understanding of the spectrum of clinical manifestations of this underrecognized familial cerebrovascular disorder.     

Lymphocytotoxins in infectious mononucleosis: a non-cytotoxic effect on their cytotoxicity in vitro

The lymphocytotoxic activity (LCA) of sera from patients with infectious mononucleosis (IM) was tested against lymphocytes under various experimental conditions. Firstly, lymphocytes from 11 healthy donors were preincubated with pools of normal human sera (NHS) or IM sera at 37°C and then tested for (a) reactivity with the same IM sera in a standard lymphocytotoxin assay at 15°C; (b) rosetting with various sheep erythrocyte (E) preparations (E, EA and EAC) and (c) stimulation by non-specific activators (phytohaemagglutinin, pokeweed mitogen and concanavalin A). These experiments showed that preincubation of normal cells with IM sera caused significant reduction in subsequent lymphocyte killing at 15°C (P<0·01) compared to unincubated cells or those preincubated with pooled NHS. There was no change in the binding of E, EA and EAC or mitogen stimulation following incubation. Culture of preincubated lymphocytes in lymphocytotoxin-free medium for 24 hr did not restore LCA at 15°C. Secondly, a pool of normal lymphocytes was incorporated into media containing either 2,4-dinitrophenol or sodium azide and tested for LCA against 11 acute IM sera and two NHS at both 15 and 37°C. No significant change in cell killing was observed at 15°C in the presence of these inhibitors, but there was a significant return of LCA at 37°C. Finally, normal lymphocytes and cells from two patients with IM were cultured at 37°C in lymphocytotoxin-free medium to determine the role of down-regulation of lymphocyte surface receptors in reducing autolymphocytotoxicity during the acute phase of the illness. There was no change in cell killing by IM sera after culture for 24 hr. These experiments show that lymphocytotoxic sera from patients with infectious mononucleosis interact with normal lymphocytes at 37°C without causing cell killing. This interaction caused a change in surface-binding characteristics that was not reversed by culture in ligand-free medium for 24 hr. Studies using metabolic inhibitors suggested that the failed lymphocytotoxicity at 37°C resulted, at least in part, from lymphocyte metabolism, although this did not inhibit the reaction between cytotoxic material and the lymphocyte surface.     

Gene expression and serum levels of insulin-like growth factors (IGFs) and IGF-binding proteins in a case of non-islet cell tumour hypoglycaemia

We describe a case of non-islet cell tumour hypoglycaemia (NICTH) associated with a renal cell carcinoma. Serum insulin-like growth factors (IGFs) (including IGF-II E peptide), IGF-binding proteins (IGFBPs), insulin and C-peptide were measured before and after surgical removal of the tumour. IGFBPs were visualized by Western ligand blotting. Preoperatively 'big' IGF-II and IGFBP-2 levels were raised. IGF-I, IGFBP-1 and IGFBP-3 were low, while insulin, C-peptide and GH were undetectable. These changes were reversed by 2 days postoperatively. Protease assays showed little IGFBP-3 protease activity preoperatively. Preoperatively, neutral chromatography demonstrated most of the immunoassayable IGFBP-3 in a high molecular weight form with a small amount of IGF-II. Most of the IGF-II and big IGF-II eluted in lower molecular weight forms. Postoperative samples showed a shift in IGF-II which became increasingly associated with IGFBP-3 in both low and high molecular weight complexes. By Northern blotting, expression of all species of IGF-II mRNA in the tumour was 10-fold greater than in normal human liver. The tumour did not express IGFBP-1 or IGFBP-2. IGFBP-3 was expressed in small amounts, while the expression of IGFBP-4 was two-fold higher than in liver. In conclusion, we have confirmed high levels of big IGF-II and IGFBP-2 in NICTH, changes which are reversed postoperatively. The IGF-II is derived from the tumour which overexpresses these genes but IGFBP-2 probably arises from extratumour upregulation.     

Arm crank ergometry and shoulder pain in persons with spinal cord injury

Dyson-Hudson TA, Sisto SA, Bond Q, Emmons R, Kirshblum SC. Arm crank ergometry and shoulder pain in persons with spinal cord injury.

Objective

To determine whether a primary fitness program utilizing arm crank ergometry would cause increased shoulder pain in persons with spinal cord injury (SCI).

Design

Cohort study.

Setting

Clinical research center.

Participants

People (N=23) with chronic SCI (>1y) who were participating in a weight loss study to compare the effectiveness of diet only (1000kcal/d for 12wk) versus diet with arm crank ergometry (1000kcal/d and arm crank ergometry 3 times a week for 12wk).

Intervention

Arm crank ergometry.

Main Outcome Measure

Changes in shoulder pain intensity using the Wheelchair User’s Shoulder Pain Index (WUSPI).

Results

After adjusting for baseline scores, there was no significant difference between the 2 groups on postintervention WUSPI scores (F_1,20=.85, P=.37, partial η²=.04). The strength of the relationship between group assignment (diet only vs diet and arm crank ergometry) and final WUSPI score was weak, as assessed by a partial η², with group assignment accounting for 4% of the variance on the WUSPI. The adjusted means were lower in the diet and arm crank ergometry group (mean, 7.84) than in the diet only group (mean, 12.22); however, these differences did not appear to be clinically significant.

Conclusions

A primary fitness program using arm crank ergometry does not increase shoulder pain in people with SCI who use wheelchairs. Further investigation with a larger group and what constitutes clinically significant changes on the WUSPI is warranted to confirm our results.