[Polydipsia, increasing fatigue and a huge mediastinal tumor in a 49-year-old woman]. / Polydipsie, zunehmende Müdigkeit und große mediastinale Raumforderung bei einer 49-jährigen Patientin.

A 49-year-old woman presented with unspecific symptoms including polydipsia, increasing fatigue for several weeks, and vague abdominal pain. Serum calcium (5.30 mmol/l; normal range 2.00-2.60) and parathyroid hormone levels (> 2500.0 ng/l; normal range 15.0-68.0) were extremely elevated. Imaging studies showed a huge mediastinal tumor. Based on these findings a hypercalcemic crisis caused by primary hyperparathyroidism was diagnosed. After intensive care treatment and further diagnostic procedures, the patient's parathyroid adenoma was removed by parathyroidectomy. The postoperative course was uneventful.

The effect of hospital setting and teaching status on outcomes after hip fracture.

This study used the National Inpatient Sample database for 1998 through 2003 to identify patients who were aged 65 years or older and had undergone surgical treatment for an isolated femoral neck or intertrochanteric hip fracture. Hospital setting (urban vs rural) and teaching status (teaching vs nonteaching) were the primary independent variables studied. The final cohort consisted of 226,239 patients. Overall in-hospital mortality was 2.6%. Higher in-hospital mortality risk was associated with increased number of in-hospital complications, increased number of comorbidities, male sex, longer surgical delay, and age 85 years or older. The overall surgical complication rate was 10.1%; there was little effect for any of the studied factors on risk for in-hospital complication. Contrary to expectation, hospital setting and teaching status were generally not as relevant to in-hospital outcomes as other factors were.

Dropped-head syndrome resulting from injury to the central spinal cord at the upper cervical level.

There are many causes of paraspinal muscle weakness which give rise to the dropped-head syndrome. In the upper cervical spine the central portion of the spinal cord innervates the cervical paraspinal muscles. Dropped-head syndrome resulting from injury to the central spinal cord at this level has not previously been described. We report two patients who were treated acutely for this condition. Both presented with weakness in the upper limbs and paraspinal cervical musculature after a fracture of C2. Despite improvement in the strength of the upper limbs, the paraspinal muscle weakness persisted in both patients. One ultimately underwent cervicothoracic fusion to treat her dropped-head syndrome. While the cause of the dropped-head syndrome cannot be definitively ascribed to the injuries to the spinal cord, this pattern is consistent with the known patho-anatomical mechanisms of both injury to the central spinal cord and dropped-head syndrome.

Tauroursodeoxycholic acid exerts anticholestatic effects by a cooperative cPKC alpha-/PKA-dependent mechanism in rat liver.

OBJECTIVE: Ursodeoxycholic acid (UDCA) exerts anticholestatic effects in part by protein kinase C (PKC)-dependent mechanisms. Its taurine conjugate, TUDCA, is a cPKC alpha agonist. We tested whether protein kinase A (PKA) might contribute to the anticholestatic action of TUDCA via cooperative cPKC alpha-/PKA-dependent mechanisms in taurolithocholic acid (TLCA)-induced cholestasis. METHODS: In perfused rat liver, bile flow was determined gravimetrically, organic anion secretion spectrophotometrically, lactate dehydrogenase (LDH) release enzymatically, cAMP response-element binding protein (CREB) phosphorylation by immunoblotting, and cAMP by immunoassay. PKC/PKA inhibitors were tested radiochemically. In vitro phosphorylation of the conjugate export pump, Mrp2/Abcc2, was studied in rat hepatocytes and human Hep-G2 hepatoma cells. RESULTS: In livers treated with TLCA (10 micromol/l)+TUDCA (25 micromol/l), combined inhibition of cPKC by the cPKC-selective inhibitor Gö6976 (100 nmol/l) or the non-selective PKC inhibitor staurosporine (10 nmol/l) and of PKA by H89 (100 nmol/l) reduced bile flow by 36% (p<0.05) and 48% (p<0.01), and secretion of the Mrp2/Abcc2 substrate, 2,4-dinitrophenyl-S-glutathione, by 31% (p<0.05) and 41% (p<0.01), respectively; bile flow was unaffected in control livers or livers treated with TUDCA only or TLCA+taurocholic acid. Inhibition of cPKC or PKA alone did not affect the anticholestatic action of TUDCA. Hepatic cAMP levels and CREB phosphorylation as readout of PKA activity were unaffected by the bile acids tested, suggesting a permissive effect of PKA for the anticholestatic action of TUDCA. Rat and human hepatocellular Mrp2 were phosphorylated by phorbol ester pretreatment and recombinant cPKC alpha, nPKC epsilon, and PKA, respectively, in a staurosporine-sensitive manner. CONCLUSION: UDCA conjugates exert their anticholestatic action in bile acid-induced cholestasis in part via cooperative post-translational cPKC alpha-/PKA-dependent mechanisms. Hepatocellular Mrp2 may be one target of bile acid-induced kinase activation.

Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer.

This multicentre phase II study evaluated the efficacy and safety of preoperative capecitabine plus oxaliplatin and radiotherapy (RT) in patients with locally advanced rectal cancer (T3/T4 rectal adenocarcinoma with or without nodal involvement). Treatment consisted of one cycle of XELOX (capecitabine 1000 mg m(-2) bid on days 1-14 and oxaliplatin 130 mg m(-2) on day 1), followed by RT (1.8 Gy fractions 5 days per week for 5 weeks) plus CAPOX (capecitabine 825 mg m(-2) bid on days 22-35 and 43-56, and oxaliplatin 50 mg m(-2) on days 22, 29, 43 and 50). Surgery was recommended 5 weeks after completion of chemoradiotherapy. The primary end point was pathological complete tumour response (pCR). Sixty patients were enrolled. In the intent-to-treat population, the pCR rate was 23% (95% CI: 13-36%). 58 patients underwent surgery; R0 resection was achieved in 57 (98%) patients, including all 5 patients with T4 tumours. Sphincter preservation was achieved in 49 (84%) patients. Tumour and/or nodal downstaging was observed in 39 (65%) patients. The most common grade 3/4 adverse events were diarrhoea (20%) and lymphocytopaenia (43%). Preoperative capecitabine, oxaliplatin and RT achieved encouraging rates of pCR, R0 resection, sphincter preservation and tumour downstaging in patients with locally advanced rectal cancer.

Sulfasalazine reduces bile acid induced apoptosis in human hepatoma cells and perfused rat livers.

BACKGROUND: Bile acid induced apoptosis in hepatocytes can be antagonised by nuclear factor kappaB (NFkappaB) dependent survival pathways. Sulfasalazine modulates NFkappaB in different cell types. We aimed to determine the effects of sulfasalazine and its metabolites sulfapyridine and 5-aminosalicylic acid (5-ASA) on bile acid induced apoptosis in hepatocytes. METHODS: Apoptosis was determined by caspase assays and immunoblotting, NFkappaB activation by electrophoretic mobility shift assay and reporter gene assays, generation of reactive oxygen species (ROS) fluorometrically, bile secretion gravimetrically, and bile acid uptake radiochemically and by gas chromatography in HepG2-Ntcp cells and isolated perfused rat livers. RESULTS: Glycochenodeoxycholic acid (GCDCA 75 micromol/l) induced apoptosis was reduced by sulfasalazine dose dependently (1-1000 micromol/l) in HepG2-Ntcp cells whereas its metabolites 5-ASA and sulfapyridine had no effect. Sulfasalazine significantly reduced GCDCA induced activation of caspases 9 and 3. In addition, sulfasalazine activated NFkappaB and decreased GCDCA induced generation of ROS. Bile acid uptake was competitively inhibited by sulfasalazine. In perfused rat livers, GCDCA (25 micromol/l) induced liver injury and extensive hepatocyte apoptosis were significantly reduced by simultaneous administration of 100 micromol/l sulfasalazine: lactate dehydrogenase and glutamate-pyruvate transaminase activities were reduced by 82% and 87%, respectively, and apoptotic hepatocytes were observed only occasionally. GCDCA uptake was reduced by 45 (5)% when sulfasalazine was coadministered. However, when 50% of GCDCA (12.5 micromol/l) was administered alone, marked hepatocyte apoptosis and liver injury were again observed, questioning the impact of reduced GCDCA uptake for the antiapoptotic effect of sulfasalazine. CONCLUSION: Sulfasalazine is a potent inhibitor of GCDCA induced hepatocyte apoptosis in vitro and in the intact liver.

The bile acid-activated phosphatidylinositol 3-kinase pathway inhibits Fas apoptosis upstream of bid in rodent hepatocytes.

BACKGROUND & AIMS: Bile acids differentially modulate hepatocyte injury in cholestasis. Although glycochenodeoxycholate (GCDC) induces Fas-mediated hepatocyte apoptosis, taurochenodeoxycholate (TCDC) simultaneously activates a phosphatidylinositol 3-kinase (PI 3-K)-mediated survival pathway blocking Fas apoptosis. In this study, the mechanisms by which the TCDC/PI 3-K survival signal disrupts Fas signaling were examined. METHODS: Studies were performed in primary cultures of mouse hepatocytes and the bile-salt-transporting McNtcp.24 rat hepatoma cell line. RESULTS: GCDC, but not TCDC, resulted in cytochrome c release demonstrating that TCDC blocked apoptosis upstream of mitochondria. In contrast, both GCDC and TCDC treatment resulted in Fas aggregation and recruitment of a dominant-negative FADD green fluorescent protein (GFP) and C360S procaspase 8-GFP to the plasma membrane. Despite recruitment of procaspase 8 to the plasma membrane by both bile acids, only GCDC resulted in increases of caspase 8 activity and Bid-GFP mitochondrial translocation. However, when PI-3K was inhibited with wortmannin or dominant-negative PI 3-K, TCDC-induced Bid-GFP mitochondrial translocation and cytochrome c release. CONCLUSIONS: The TCDC/PI 3-K survival signal blocks Fas-mediated apoptosis by preventing caspase 8 activation and Bid mitochondrial translocation. Potentiation of this survival pathway in cholestasis has the potential to attenuate liver injury.

Hepatocyte apoptosis is a pathologic feature of human alcoholic hepatitis.

BACKGROUND/AIMS: The pathogenesis of alcoholic hepatitis (AH) remains poorly understood. Although apoptosis is now recognized as a mechanism of liver injury, the extent and mechanisms of apoptosis in human AH remain unknown. Thus, our aims were to quantify hepatocyte apoptosis in patients with AH, correlate it with disease severity, and identify the mechanisms of apoptosis induction. METHODS: Hepatocyte apoptosis was assessed in 26 patients with AH and 27 controls without liver disease using the TUNEL assay and immunohistochemistry for activated caspase 3. Liver specimens were also graded for disease severity. The expression of the death receptors, Fas and tumor necrosis factor-alpha receptor 1 (TNF-R1), was assessed by immunohistochemistry. RESULTS: In contrast to normal livers, TUNEL- and caspase 3-positive hepatocytes were readily observed in the livers of patients with AH. In the AH group, hepatocyte apoptosis was significantly higher in patients with a serum bilirubin of > 3 mg/dl. Apoptosis was also greater in grade 4 steatohepatitis. The Fas receptor was strongly expressed in hepatocytes in AH, but not in normal livers; the TNF-R1 expression was comparable in both groups. CONCLUSIONS: The present results demonstrate that hepatocyte apoptosis is significantly increased in human AH and justify therapeutic strategies aimed at inhibiting apoptosis in this disease.

NF-kappaB is activated in cholestasis and functions to reduce liver injury.

Selected bile acids activate a nuclear factor-kappa B (NF-kappaB)-dependent survival signaling cascade in cultured hepatocytes. These data suggest that in cholestasis where liver tissue bile acid concentrations are increased, NF-kappaB should be activated and inhibition of NF-kappaB should potentiate liver injury. Our aims were to test these two predictions. Cholestasis was obtained by common bile duct ligation in mice. NF-kappaB activation was demonstrated in nuclear extracts by the electrophoretic mobility gel shift assay from 3-day bile duct-ligated (BDL) mice but not in controls. Immunohistochemistry for NF-kappaB demonstrated nuclear localization in hepatocytes of BDL mice consistent with its activation in this liver cell type. Electrophoretic mobility gel shift assay and immunohistochemistry for NF-kappaB in BDL tumor necrosis factor-receptor 1 knockout mice demonstrated hepatocyte NF-kappaB activation, suggesting that tumor necrosis factor-alpha was not responsible for the activation of this transcription factor. Liver injury was assessed in BDL mice after administration of the adenovirus 5 inhibitor of kappa B superrepressor (Ad5IkappaBsr) to inhibit NF-kappaB. TUNEL-positive cells and serum alanine aminotransferase values were increased at least threefold in mice treated with the Ad5IkappaBsr versus the empty virus. Liver histology also demonstrated increased liver injury in the BDL mice treated with the Ad5IkappaBsr. In conclusion, NF-kappaB is activated in hepatocytes during obstructive cholestasis and functions to reduce liver injury.

Locoregional management of hepatocellular carcinoma. Surgical and ablation therapies.

The selection of an appropriate treatment strategy for patients with HCC depends on careful tumor staging and assessment of the underlying liver disease (Fig. 5). All patients with localized HCC (involvement of one single lobe, no vascular invasion or extrahepatic disease) should be evaluated for the potentially curative therapeutic options of partial hepatectomy or OLT. Candidates for partial hepatectomy must have no liver disease or Child's A cirrhosis, normal portal pressure, and normal serum bilirubin. For patients not meeting these criteria, OLT should be considered if there is a solitary lesion smaller than 5 cm in diameter or fewer than three lesions smaller than 3 cm. Local ablative therapies such as PEI, RFA, and TACE offer palliation for patients for whom surgical approaches are contraindicated. Percutaneous alcohol injection and RFA are minimally invasive and can be used on an outpatient basis, usually for tumor nodules smaller than 3 cm. When these therapies are used for small tumors, the survival rates can be similar to those achieved by partial hepatectomy. Transcatheter [figure: see text] arterial chemoembolization may be used as an interim treatment for patients waiting for OLT. Although TACE is often used for the palliation of large tumors, significant survival benefits have not yet been demonstrated for this indication.

[75-year-old patient with persistent abdominal complaints and vomiting during a cruise]. / 75-jährige Patientin mit persistierenden abdominellen Beschwerden und Erbrechen während einer Kreuzfahrt.

BACKGROUND: In elderly patients with gallstone disease, a gallstone ileus must be considered for unexplained abdominal pain. This is demonstrated in the following case report. CASE REPORT: A 75-year-old female patient presented with a 72-hour history of abdominal pain, nausea and vomiting. The patient's abdomen was mildly distended, although soft and nontender with bowel sounds present. Plain radiographs and ultrasound investigation of the abdomen were compatible with small bowel obstruction. To clarify the etiology, an abdominal computed tomography scan was obtained. These examinations disclosed air in the biliary tree, dilated small bowel and an impacted intraluminal abnormality in the terminal ileum compatible with a gallstone. Operative intervention confirmed the presence of a 3 cm obstructing calculus in the terminal ileum that was removed by an enterolithotomy. A two-step cholecystectomy and closure of the cholecystoduodenal fistula were performed 8 weeks later. The patient's recovery was uneventful. CONCLUSIONS: Although rare in a general population, gallstone ileus accounts for 25% of nonstrangulated small bowel obstructions in patients over the age of 65. The radiographic picture and ultrasound of small bowel obstruction and the presence of air in the biliary tree are suggestive for the diagnosis of a gallstone ileus. In our patient, the computed tomography and ultrasound findings confirmed the diagnosis and led to a prompt and directed surgical intervention. In patients with comorbid factors a two-step approach with enterolithotomy in a first and cholecystectomy in a second operation should be the therapeutic strategy of choice.

The bile acid taurochenodeoxycholate activates a phosphatidylinositol 3-kinase-dependent survival signaling cascade.

Liver injury during cholestasis reflects a balance between the effects of toxic and nontoxic bile acids. However, the critical distinction between a toxic and nontoxic bile acid remains subtle and unclear. For example, the glycine conjugate of chenodeoxycholate (GCDC) induces hepatocyte apoptosis, whereas the taurine conjugate (TCDC) does not. We hypothesized that the dissimilar cellular responses may reflect differential activation of a phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway. In the bile acid-transporting McNtcp.24 rat hepatoma cell line, TCDC, but not GCDC, stimulated PI3K activity. Consistent with this observation, inhibition of PI3K rendered TCDC cytotoxic, and constitutive activation of PI3K rendered GCDC nontoxic. Both Akt and the atypical protein kinase C isoform zeta (PKCzeta) have been implicated in PI3K-dependent survival signaling. However, TCDC activated PKCzeta, but not Akt. Moreover, inhibition of PKCzeta converted TCDC into a cytotoxic agent, whereas overexpression of wild-type PKCzeta blocked GCDC-induced apoptosis. We also demonstrate that TCDC activated nuclear factor kappaB (NF-kappaB) in a PI3K- and PKCzeta-dependent manner. Moreover, inhibition of NF-kappaB by an IkappaB super-repressor rendered TCDC cytotoxic, suggesting that NF-kappaB is also necessary to prevent the cytotoxic effects of TCDC. Collectively, these data suggest that some hydrophobic bile acids such as TCDC activate PI3K-dependent survival pathways, which prevent their otherwise inherent toxicity.

Hepatocyte apoptosis after bile duct ligation in the mouse involves Fas.

BACKGROUND & AIMS: Cholestatic liver injury results from the intrahepatic accumulation of toxic bile salts. Toxic bile salt-induced hepatocyte apoptosis in vitro is Fas dependent. The aim of this study was to ascertain if hepatocyte apoptosis in vivo during cholestasis is Fas dependent. METHODS: Studies were performed in bile duct-ligated (BDL) Fas-deficient lpr (lymphoproliferation) and wild-type mice. RESULTS: Hepatocyte apoptosis was the predominant mechanism of cell death as determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and trypan blue assays to quantitate apoptosis and necrosis. The mechanisms of hepatocyte apoptosis were dependent on the presence or absence of the Fas receptor and the duration of BDL. After BDL of 3 days' duration, increased hepatocyte apoptosis occurred only in wild-type but not lpr mice, indicating the apoptosis was Fas dependent. In contrast, after BDL of >/=7 days, hepatocyte apoptosis also occurred in lpr animals consistent with a Fas-independent mechanism of apoptosis. Hepatocyte apoptosis in BDL lpr mice was associated with an increase in Bax expression and Bax association with mitochondria. CONCLUSIONS: During extrahepatic cholestasis, hepatocyte apoptosis is mediated by Fas. However, in the absence of the Fas receptor, additional mechanisms of hepatocyte apoptosis occur. Inhibition of multiple apoptotic pathways is necessary to attenuate chronic cholestatic liver injury.

Intravenous coronary angiography with dichromography using synchrotron radiation.

Dichromography represents a digital subtraction angiography mode based on energy substraction which allows imaging of fast moving subjects like the heart. For logarithmic subtraction 2 images with X-rays just below and above the iodine K-edge (33.17 keV) are simultaneously obtained in a line scan mode. Monochromatic X-rays of sufficient intensity to visualize coronary arteries of 1 mm diameter with extremely low iodine concentrations (1 mg/cm2) after venous injection is only provided by synchrotron radiation. The system NIKOS (non-invasive coronary arteriography with synchrotron radiation) at the Deutsches Elektronen Synchrotron (DESY) consists of 6 components: a wiggler, a monochromator, a safety system, a scanning device, a detector and a computer system. After experimental studies in dogs patients are imaged since 1990. Initial results demonstrate feasibility and safety of synchrotron radiation coronary angiography. Large scale studies are designed to further evaluate sensitivity and specificity. When compact synchrotron radiation sources become available, this technique could be used for follow-up studies and for evaluation of certain high coronary risk populations.

Joint-derived T cells in rheumatoid arthritis react with self-immunoglobulin heavy chains or immunoglobulin-binding proteins that copurify with immunoglobulin.

Rheumatoid arthritis patients were found to have CD4+ T cells that proliferate in response to autologous synovial fluid and plasma. T cell clones and polyclonal T cell lines were found to respond to antigen(s) eluted from protein A Sepharose and anti-human immunoglobulin (Ig) antibody Sepharose. The antigen(s) was further resolved to fractions that contained intact Ig or Ig heavy chain since the T cells responded to > 100 kDa and 40-60 kDa polypeptides derived from purified Ig under nonreducing and reducing conditions, respectively. These results indicated that the antigen(s) is either Ig heavy chain or Ig-binding proteins that copurify with Ig and Ig subunits. Pepsin and papain digestion of the antigenic fractions eluted from protein A destroyed the T cell reactivity. Since most Fab regions are resistant to these enzymes, further analyses are required to localize the antigenic epitope(s). The presence of Ig- or Ig-antigen complex-reactive T cells in arthritic joints implies that B cells expressing anti-Ig antibody (i.e. rheumatoid factor) may play an important role in antigen presentation to autoreactive T cells.

[The value of spiral computed tomography in the imaging of aortocoronary bypass vessels]. / Validität der Spiral-Computertomographie bei der Darstellung aortokoronarer Bypass-Gefässe.

Spiral computer tomography (Sp-CT) was performed on 25 patients with 81 aorto-coronary bypasses, with persistent symptoms, following selective coronary angiography. The purpose was to determine to what extent Sp-CT is able to demonstrate patency or occlusion of individual bypasses. From the raw data, transverse sections and standardised 3D reconstructions were obtained. Statistical evaluation showed a sensitivity of 93% and a specificity of 100% with regard to patency. Sp-CT provides optimal contrast and complete demonstration of the bypass without movement artifacts from respiration. 3D reconstructions aid in the evaluation of complex anatomical situations but occasionally lead to incorrect diagnosis of stenoses or occlusions. Compared with other non-invasive procedures (conventional CT and NMR) Sp-CT has proved significantly better for the evaluation of bypass occlusions. Sp-CT cannot completely replace angiography but in some cases may be an acceptable alternative.

Reactivity of human gamma delta T cells to staphylococcal enterotoxins: a restricted reaction pattern mediated by two distinct recognition pathways.

Staphylococcal enterotoxins (SEs) are known superantigens for T cells expressing the alpha beta T-cell receptor (TCR). They bind to MHC class II molecules on antigen-presenting cells and can subsequently trigger T-cell responses by binding to V beta-gene products. The reactivity of gamma delta T cells with enterotoxins is less well defined although both proliferative and cytotoxic responses have been described. In the present study we have tested the cytotoxic reactivity of a panel of 41 gamma delta T-cell clones against target cells coated with the enterotoxins SEA, SEB, SEC1, SEC2, SEC3, SED, SEE or TSST. Three reaction patterns were observed with the gamma delta T-cell clones: (1) clones that specifically lysed SEA-coated target cells only; (2) clones that specifically lysed SEE-coated target cells only, and (3) clones that specifically lysed SEA-coated target cells only in the presence of certain human sera. The presence of SEA-specific antibodies in such human sera could be demonstrated. Moreover, gamma delta T-cell clones of this third category expressed the IgG FcRIII (CD16) which indicates that these clones are capable of mediating antibody-dependent cellular cytotoxicity towards SEA-coated target cells. Thus, the cytotoxic response of gamma delta T cells to SEs is mediated by two distinct pathways: an antibody-independent and an antibody-dependent pathway. The antibody-independent reactivity of gamma delta T cells was directed to either SEA or SEE, whereas antibody-dependent reactivity was found only towards SEA. The capacity of gamma delta T-cell clones to respond to stimulation with SEs, combined with their high cytolytic capacity in vitro, suggests that these cells can be involved in SE-directed immune responses and efficiently kill SE-coated target cells in vivo.

Gamma delta T cell reactivity towards bacterial superantigens.

Human TCR gamma delta positive T cells can proliferate in response to stimulation with staphylococcal enterotoxins (SEs) or mediate lysis of SE pulsed target cells. In the small number of studies reported, the proliferative response of gamma delta T cells was limited to V gamma 9 negative cells and, in vitro, such responses do not require the presence of MHC class II molecules for antigen presentation. Proliferative responses have been found after stimulation with SEA, SEB and TSST. The cytolytic activity of gamma delta T cells can be mediated by two different mechanisms: either gamma delta T cells specifically interact with SEA pulsed target cells--this is most likely TCR mediated recognition--or gamma delta T cells mediate antibody dependent cellular cytotoxicity (ADCC). This latter reactivity depends on Fc-receptor expression by the gamma delta T cell clones and the presence of SE specific antibodies during the assay. So far cytotoxic gamma delta T cell reactivity has only been found against the highly homologous enterotoxins SEA and SEE. Finally, HLA-class II positive gamma delta T cell clones can present SE to other SE reactive T cells but appear to be relatively resistant to T cell mediated lysis. Taken together, TCR gamma delta positive T cells are able to respond to a number of bacterial superantigens and may therefore be involved in local immune responses to such antigens. This may be especially relevant for those gamma delta T cell subpopulations that are preferentially found in the (intestinal) epithelia where exposure to bacterial superantigens is likely to occur.