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Biomedical subjects

A Schütz

Publications and source records attributed to A Schütz.

At least 19 recordsLinked to original sources

Lead in plasma and whole blood from lead-exposed children.

In 31 children exposed to lead and 13 considerably less exposed children ("unexposed"), the plasma (Pb-P) concentrations ranged from 0.46 to 18.4 (median, 2.4) and from 0.14 to 0.38 (median, 0.21) microg/L, respectively. Corresponding whole-blood concentrations (Pb-B) were 99-920 (median, 370) and 39-120 (median, 66) microg/L, respectively. The relation between Pb-B and Pb-P was nonlinear; when Pb-P rose, the Pb-B increased relatively less. There was a close association between Pb-B and log Pb-P (r=0.95; P=0.0001). When these data were compared to previous data on adults, there was no major difference between children and adults in the Pb-B/Pb-P relation. Free erythrocyte protoporphyrins in blood were associated with Pb-P (r=0.75; P=0.0001) and Pb-B (r=0.90; P=0.0001). Also, there was an association between blood-hemoglobin concentration and Pb-P in both exposed (r=-0.67; P=0.0001) and unexposed (r=-0.67; P=0.01) children; the corresponding figures for Pb-B were r=-0.42; P=0.02, and r=-0.80; P=0.001, respectively. Thus, at least with regard to toxicity on hematopoiesis at high lead levels, Pb-P may be a more relevant indicator of exposure and risk than Pb-B. Because the curved Pb-B/Pb-P relation indicates a saturation of binding sites for lead in red cells, exposure and risk at high lead levels may easily be underestimated from Pb-B data.

Adolescent

Lead exposure and hearing effects in children in Katowice, Poland.

The objective of the study was to investigate the relationship between lead exposure and hearing in children in the Katowice region, an industrial area in Poland. Blood lead was determined using inductively coupled plasma mass spectrometry, with appropriate quality control. The concentrations of lead in blood (B-Pb) in 155 children, aged 4-14, ranged from 19 to 281 microg/L (0.09 to 1.4 micromol/L), with a median of 72 microg/L (0.34 micromol/L). The hearing thresholds increased significantly with increasing blood lead levels at all investigated frequencies (0.5, 1, 2, 4, 6, and 8 kHz). The relationship also remained significant for B-Pb below 100 microg/L (0.48 micomol/L; n=107). The brainstem auditory evoked potential latency of wave I was significantly increased (also after adjustment for age) in the group of children with the highest blood lead levels (B-Pb above 100 microg/L, 0.48 micromol/L; n=51), compared to the group with the lowest ones (B-Pb below 46 microg/L, 0.22 micromol/L; n=51). The audiometric results clearly indicate that auditory function in children is impaired at a blood lead concentration even below 100 microg/L (0.5 micromol/L).

Adolescent

Chelated lead in relation to lead in bone and ALAD genotype.

In order to assess whether lead in bone is available for chelation by 2,3 meso-dimercaptosuccinic acid (DMSA), 21 workers (10 active and 11 retired) from a secondary lead smeltery were studied. A morning urine sample was obtained from all participants, followed by ingestion of 10 mg per kg body weight of the chelating agent DMSA. All urine produced during the following 24 h was collected in consecutive 6- and 18-h portions. Concentrations of lead in blood (B-Pb) and urine were determined by flameless atomic absorption spectrometry (AAS), in plasma (P-Pb) by inductively coupled plasma mass spectrometry (ICP-MS), and in finger bone (Bone-Pb) by K X-ray fluorescence technique (XRF). DMSA-chelatable lead excreted in the 24-h portion correlated well with the excretion in the 6-h portion (U-Pb6h; rs=0.95; P<0.001). U-Pb6h showed a non-linear relationship to B-Pb (rs=0.84; P<0.001) and linear relationships to P-Pb (rs=0. 91; P<0.001) and lead in morning urine (rs=0.95; P<0.001). In active workers, but not in retired ones, P-Pb and U-Pb6h showed some relationship to Bone-Pb. In alternative multiple regression models B-Pb or P-Pb were both significant predictors of U-Pb6h, while Bone-Pb did not significantly improve the models. It can, thus, be concluded that DMSA-chelatable lead mainly reflects lead concentrations in blood, soft tissues, and possibly also trabecular bone. It is not a good index of total body burden and long-term exposure. For such estimations cortical Bone-Pb is more valid, as it contains the major fraction of long-term accumulated lead in the body. Further, the mobilization test did not give better information than measurements of lead levels in blood, plasma, or urine without chelation.

Age Factors

Less invasive, continuous hemodynamic monitoring during minimally invasive coronary surgery.

BACKGROUND: Minimally invasive coronary surgery has gained more and more clinical acceptance. A clear contrast to the minimally invasive idea is the highly invasive pulmonary artery catheter used for hemodynamic monitoring during the operation. We evaluated a less invasive device which calculates cardiac output (CO) and hemodynamics based on arterial pulse-contour analysis. METHODS: In 20 patients revascularized by the off-pump technique with the octopus system, agreement of CO by pulse-contour was compared to pulmonary arterial and femoral arterial thermodilution and hemodynamic alterations during the operation were recorded. Pulse-contour CO is computed by measuring the area under the arterial pressure waveform and dividing it by aortic impedance. Aortic impedance is determined by an arterial thermodilution at the onset of the system. RESULTS: Correlation of pulmonary arterial and arterial thermodilution CO to pulse-contour CO was 0.91 and 0.90 respectively (both p<0.01). Coefficients of variations were 6.2% and 6.7%. The bias was 0.1 L per minute and standard deviations were 0.42 L per minute and 0.55 L per minute. Hemodynamic changes during the operations were seen mainly during the distal anastomosis of the first diagonal branch; only slight changes occurred during the anastomosis of the left anterior descending coronary artery. CONCLUSIONS: Arterial pulse-contour analysis is easy to use and minimally invasive, thus qualifies as a reliable routine monitoring tool during minimally invasive coronary surgery with tissue stabilizers.

Aged

Intraoperative local fibrinolysis as emergency therapy after early coronary artery bypass thrombosis.

OBJECTIVE: Acute graft occlusion early postoperatively after coronary artery bypass grafting (CABG) is a rare but dramatic complication, frequently making resuscitation necessary. Emergency reoperation with reanastomosing of the concerning grafts is the normal procedure to restrict the otherwise unavoidable myocardial damage. Mortality in these cases is up to 50%. Due to this unsatisfying situation, we perform since 1995 in such cases an adjuvant intraoperative intracoronary installed fibrinolysis with recombinant tissue type plasminogen activator (rt-PA; alteplase). METHODS: Between 1/1994 and 8/1998, 4231 patients underwent CABG. In 18 of these patients, emergency reoperation within the first 12 h after CABG due to clinical signs of acute myocardial infarction was necessary. In nine of the patients (group II) additionally intraoperative rt-PA lysis of the involved vessel/s has been performed. When the peripheral anastomosis was reopened and the thrombotic material was removed, we inserted for this a left atrial-catheter (LA-catheter) of 1.2 mm in diameter, into the coronary artery. Then we administered within 3-5 min, up to 100 mg rt-PA (t1/2: 5-9 min.) locally into the vessel. All patients were treated postoperatively with acetylsalicyl acid (ASA) and heparine. RESULTS: In group I (n = 9; seven males, two females) without thrombolytic therapy, 78% of the patients (n = 7) could not have been prevented from large myocardial infarction despite emergency reoperation. Three of these patients died during or early after reintervention. In group II with fibrinolytic therapy (n = 9) three of the patients developed Q-wave myocardial infarction following reoperation. None of the patients died. Creatinkinase maximum were in group I significantly higher than in group II (group I: CK = 1254 units/I, CK-MB = 197 units/l; group II: CK = 502 units/l, CK-MB = 61 units/l; P < 0.01). Postoperative bleeding was considerable elevated in both groups. In group I, 832 ml/24 h (375-1420 ml), in group II 1164 ml/24 h (520-1560 ml). Lysis-associated complications were not observed. CONCLUSIONS: Reoperation of patients with acute thrombotic bypass occlusion after CABG is characterized by a high mortality and morbidity. If additionally fibrinolysis is performed, a sufficient myocardial perfusion seems to be restored. A short half-life in combination with the presented non-systemic application technique of rt-PA seem to prevent unpredictable bleeding. Rt-PA lysis apparently contributes very effectively to the restoration of the macro- and microcirculation within the infarct-related area. Thrombolytic therapy during cardiac surgery with rt-PA is feasible, its application easy and harmful complications are not seen.

Aged

Surgical versus medical care for postoperative cardiac surgical patients at the general ward.

OBJECTIVES: To shorten hospital stay after cardiac surgery, several risk factors have been defined to identify patients who can be discharged early. These risk factors are dependant on the patient; no studies exist on the influence of the treating physician himself on postoperative patient stay. METHODS: In a university affiliated cardiac surgical clinic we investigated patients who were postoperatively treated either on medical wards with no cardiac surgeon's presence or on a cardiac surgical ward; at both types of wards physicians had several years experience with cardiac surgical patients. Taking several risk factors for postoperative morbidity into account, postoperative length of stay and incidence of wound healing complications have been compared. RESULTS: Within a 3-month period, 84 patients were treated at the cardiac surgical ward, 102 patients at the medical wards. Risk factors for postoperative morbidity were present in 87% of patients, statistically independent of postoperative wards. Although demographic data and median ICU-stay of both patient groups was comparable, the median post-ICU stay was 9 days at the surgical and 13 days at the medical wards (P < 0.0001). Incidence of wound healing complication was higher (19.6%) at the medical wards than at the surgical ward (10.7%), without reaching statistical significance. CONCLUSION: As patients at the respective wards were statistically not different, the difference in post-ICU stay, infection and costs must depend on the treating physicians. As a consequence, postoperative care for cardiac surgical patients in all cases should include direct cardiac surgical participation.

Aged

[Quantitative gas chromatography-mass spectrometry determination of pentaerythrityl tetranitrate metabolites pentaerythrityl trinitrate, pentaerythrityl dinitrate and pentaerythrityl in human plasma].

Assay methods based on gas chromatography/mass spectroscopy (GC-MS) may be used to measure PE1N (pentaerithrityl mononitrate, CAS 1607-00-7), PE2N (pentaerithrityl dinitrate, CAS 1607-01-8) and intermediate pentaerithrityltrinitrate (PE3N, CAS 1607-17-6) in human plasma. Based on this method a simplified method to quantify the metabolites of PETN (pentaerithrityl tetranitrate, CAS 78-11-5, Pentalong) is described. In the present study a consistent method to extract the metabolites of human plasma and following derivatisation is described. Since PE1N can be quantified up to 150 ng/ml, PE2N and PE3N up to 30 ng/ml in human plasma, a dilution of the plasma samples can be avoided. The mean recovery rate is not so high as in other described methods, and inaccuracy is about 10%. Therefore a calibration range between 0.2-30 ng/ml of PE2N and 1-150 ng/ml of PE1N has to be considered. The described method offers an alternative and applicable option to quantify the PETN-metabolites and elucidate their part as NO-donors.

Biotransformation

Serum mercury concentration in relation to survival, symptoms, and diseases: results from the prospective population study of women in Gothenburg, Sweden.

A prospective population study of women in Gothenburg, Sweden was started in 1968-69 and comprised 1462 women aged 38, 46, 50, 54, or 60 years at baseline. Follow-up studies were carried out in 1974-75, 1980-81, and 1992-93. The baseline study included an extensive medical and dental examination. Serum mercury concentration (beta-HG) was determined in deep-frozen samples from all participants in 1968-69 and in a random subsample of sera from participants in 1980-81, about 20 years after the baseline examination. S-Hg was statistically significantly correlated with number of amalgam fillings at both examinations. Of 30 defined symptoms and 4 different clusters of symptoms, no one was independently correlated with S-Hg measured in the samples from 1968-69, while there was a negative statistically significant correlation with over-exertion and poor appetite in 1980-81. Blood hemoglobin and serum B-12 concentrations in 1968-69 were statistically significantly and positively correlated with S-Hg, while erythrocyte sedimentation rate and the serum concentrations of potassium and triglycerides were significantly and negatively correlated with S-Hg, also after including potential confounders. Blood hematocrit examined in 1980-81 was negatively correlated with S-Hg. When including potential confounders, serum IgA was also statistically significantly correlated with S-Hg, but not in univariate analysis. No statistically significant correlation was observed between S-Hg, on the one hand, and the incidence of diabetes, myocardial infarction, stroke, or cancer on the other, while a statistically significant negative correlation was observed with overall mortality when age and education were included as background variables. There were some correlations between biological variables and S-Hg, probably of no negative clinical significance, and we conclude that there is no association between disease and S-Hg on a population basis in middle-aged and older women.

Adult

Comparison of different double immunostaining protocols for paraffin embedded liver tissue.

Most of the double immunostaining protocols that have been introduced so far have been developed for application on fresh frozen material or based on different species antibodies. In liver tissue, general problems of double immunostaining techniques are further complicated by tissue-specific difficulties, such as necrosis or high intracellular protein content. To assess a reliable double immunostaining protocol for archived, paraffin embedded liver tissue, different protocols based on the use of same species primary antibodies were evaluated in terms of sensitivity, specificity and non-specific background staining in pathological liver specimens. We compared peroxidase-anti-peroxidase, alkaline phosphatase-anti-alkaline phosphatase (PAP/APAP), labelled-avidin-biotin (LAB/LAB) and digoxigenin-anti-digoxigenin (dig-a-dig/PAP) techniques using different cytokeratin antibodies and an antibody against PCNA. Comparison of the double immunostaining techniques revealed a high sensitivity and specificity in all procedures. Sections, which were stained employing PAP/APAP-technique, displayed a higher background staining compared to sections which were treated with the LAB/LAB or dig-a-dig/PAP protocol. In contrast to the dig-a-dig/PAP protocol, the LAB/LAB technique provides a better time/cost relationship. Therefore, we would like to recommend a modified LAB/LAB protocol for simultaneous detection of different antigens in archived liver tissue.

Animals

Scintigraphy and immunohistology of antimyosin-Fab during graft rejection.

Up to now, the cellular localization pattern of monoclonal antimyosin antibodies (AMA) during acute rejection has not been described. Focused on this the authors made immunohistochemical and scintigraphic studies (AMS) with AMA in an animal transplantation model. Heterotopic cervical heart transplantation was performed in 12 mongrel dogs. Immunosuppression consisted of triple drug therapy. As standard the grafts were examined by daily transmural biopsies and routine histology. Dependent on the daily biopsy results, 0.5 mg of indium 111 ((111)In)-labeled AMA-Fab was injected. Subsequently every 2 hours transmural biopsy cylinders were taken out of the right ventricle and examined in indirect peroxidase staining technique. Forty-eight hours after AMA injection, scintigraphy in single photon emission computed tomography (SPECT) technique (AMS) was carried out and the heart-to-lung ratio (H/L-ratio) was calculated. The immunohistochemical maximum of AMA accumulation could be found 20 to 72 hours after AMA injection. This means that a scintigraphic examination should be done earlier than 20 hours and later than 3 days after injection. Dependent on the grades of bioptic rejection diagnosis a specific morphologic AMA localization was seen (grade I+II intercellular and slightly intracellular detection of AMA, grade III strongly intracellular and in particular perinuclear accumulation of the antibody, p<0.01). Moreover, the authors found a good correlation between scintigraphic H/L-ratio results and the corresponding histologic findings (grade I: H/L = 2.1 +/- 0.2; grade II: H/L = 3.1 +/- 0.2; grade III: H/L = 3.5 +/- 0.3; n = 19; p<0.02). The recently described positive AMS scans even in cases of mild rejection seem to be subject to an intercellular AMA localization. This typical AMA morphology during mild rejection favors the theory of the pore-forming protein allowing the efflux of myosin fragments as effector mechanism of cytotoxic lymphocytes in the early phase of acute rejection. The immunohistochemical AMA examination could explain the present discrepancy between positive AMS results of an intracellular protein in cases of mild or moderate acute rejection when visible cellular damage in the corresponding routine histology is absent.

Animals

Cadmium, mercury, and lead in kidney cortex of the general Swedish population: a study of biopsies from living kidney donors.

Cadmium, mercury, and lead concentrations were determined in deep-frozen kidney cortex biopsies taken from 36 living, healthy Swedish kidney donors (18 males and 18 females), who were 30-71 (mean 53) years of age. Information about occupation, smoking, the presence of dental amalgam, and fish consumption could be obtained for 27 of the donors. The samples (median dry weight 0.74 mg) were analyzed using inductively coupled plasma mass spectrometry, and the results were transformed to wet-weight concentrations. The median kidney Cd was 17 micrograms/g (95% confidence interval, 14-23 micrograms/g), which was similar in males and females. In 10 active smokers, the median kidney Cd was 24 micrograms/g, and in 12 who never smoked, it was 17 micrograms/g. The median kidney Hg was 0.29 micrograms/g, with higher levels in females (median 0.54 micrograms/g) than in males (median 0.16 micrograms/g). Subjects with amalgam fillings had higher kidney Hg (median 0.47 micrograms/g, n = 20) than those without dental amalgam (median 0.15 micrograms;g/g, n = 6), but kidney Hg was below the detection limit in some samples. Nearly half of the samples had kidney Pb below the detection limit. The median kidney Pb was estimated as 0. 14 micrograms/g. This is the first study of heavy metals in kidney cortex of living, healthy subjects, and the results are relatively similar to those of a few previous autopsy studies, indicating that results from autopsy cases are not seriously biased in relation to kidney metal concentrations in the general population. Cd concentrations in those who never smoked were relatively high, indicating considerable Cd intake from the diet in Sweden. The effect of dental amalgam on kidney Hg was as expected, although the reason for the difference in Hg levels between males and females is unclear.

Adult

Endovascular repair of aortic aneurysms: treatment of complications.

PURPOSE: To evaluate the use of interventional procedures for treating complications following endovascular repair of aortic aneurysms. METHODS: Fifty-five patients (49 men; mean age 67.5 years) underwent endoluminal stent-graft repair of traumatic (n = 4) or arteriosclerotic (n = 51) aortic aneurysms in the thoracic (n = 3) or infrarenal (n = 52) aorta. Follow-up of therapeutic success included periodic clinical examination, angiography, and spiral computed tomography. RESULTS: Discounting the 25 (45%) cases of postimplantation syndrome that did not require treatment, there were 22 complications observed in 20 (36%) patients over a mean 10-month follow-up (range 1 to 27). There were 2 transrenal endograft maldeployments, 1 case of twisted graft limbs, 2 access site problems (1 patient), 12 endoleaks (11 patients), 1 late graft limb thrombosis, 1 symptomatic internal iliac artery occlusion, 2 myocardial infarctions, and 1 transient psychosis. Seven (13%) patients did not undergo specific therapy, while 4 (7%) required operation (2 crossover bypass grafts, 1 suture revision, and 1 graft replacement). Among 9 (16%) patients treated with interventional techniques, 7 underwent percutaneous coil embolization for 8 endoleaks (7 successfully resolved). One late stent-graft disconnection required an additional stent-graft, and 1 of the 2 malpositioned endografts was repositioned. All patients remain alive with no increase in the diameter of the aneurysm in any patient. CONCLUSIONS: Technical problems resulting from the endovascular repair of aortic aneurysms often respond to interventional treatment.

Adult

[Stent implantation after thrombectomy of pelvic veins. Indications, results].

PURPOSE: Retrospective study on frequency of iliac venous stenoses that are cause (venous spur) or consequence (postoperative or postthrombotic) of iliofemoral thrombosis, and on the results of interventional treatment. METHODS: From 1990 through 1996, 76 patients were operated on for acute iliac vein thromboses. All patients had transfemoral venous thrombectomy with creation of an inguinal av-fistula. Immediate results of thrombectomy were documented by intraoperative completion venogram. Since 1995 venous spurs eventually detected during thrombectomy were immediately treated by stent implantation. Before scheduled closure of the av-fistula at three months, cross-over arteriovenography was performed. Additional significant iliofemoral venous stenoses were also treated interventionally at this time. RESULTS: 42 hemodynamically significant iliofemoral venous stenoses were found in 38 (50%) patients. Intraoperative phlebography revealed left common iliac vein obstructions suggestive of venous spurs in 30 patients (49% of left-sided thromboses). At three months, five patients (7%) had postthrombotic iliac vein stenoses, and seven patients (9%) had postoperative common femoral vein stenoses. A total of 26 stents were implanted into 20 stenoses (eight spurs, all postthrombotic and postoperative stenoses). There was an acute re-occlusion due to a technical error during stent implantation. In all other patients, the venous lumen could be completely restored. Three of four re-stenoses (at 3, 4, 7, and 12 months) were successfully treated by another intervention. We observed one late failure at 60 months. Cumulative primary (secondary) five-year patency rate (Kaplan-Meier) is 72% (88%). CONCLUSION: For venous spurs as well as for postthrombotic or postoperative venous stenoses, stent implantation can be recommended as a simple, safe, and durable means to prevent rethrombosis.

Adolescent

Environmental health in the Baltic region--toxic metals.

Recent reports on concentrations of lead, cadmium, methylmercury, arsenic and nickel in some biological media in populations in the Baltic region are reviewed. In particular, children in parts of Poland, the Czech Republic, and Germany have uptakes of lead sufficient to cause adverse effects on the central nervous system and kidneys. Cadmium exposure is also high in Poland. Slight cadmium-induced effects on the kidneys have been reported from Germany and Sweden. Methylmercury uptake is dependent upon the intake of fish, in particular from contaminated lakes and rivers in Sweden and Finland, as well as the eastern coast of the Baltic Sea. There are some indications of immunotoxic effects associated with the intake of such fish. However, fish also contain other immunomodulating agents. Exposure to arsenic seems to be low everywhere in the Baltic region. There is high nickel exposure in northern Russia.

Adolescent

[Magnetic resonance tomography of the pancreas].

The following publication is an overview looking at the diagnostic possibilities of magnetic resonance imaging regarding diseases of the pancreas and showing image examples. We emphasize new techniques like the MRCP showing meaningful indications and diagnostic limitations.

Acute Disease

Enhanced generation of cytotoxic T lymphocytes using recombinant vaccinia virus expressing human tumor-associated antigens and B7 costimulatory molecules.

In this work, we addressed the possibility to enhance the "in vitro" generation of CTLs recognizing tumor-associated antigens (TAAs) by using an inactivated recombinant vaccinia virus encoding B7.1 and B7.2 costimulatory molecules (rVV-B7.1/2). Antigen presenting cells (APCs) infected by rVV-B7.1/2 and pulsed with MART-1/Melan-A27-35 HLA-A2.1-restricted peptide induced significantly higher specific cytotoxic activity than peptide-loaded APCs infected by wild-type VV, both in VV-sensitized and naive donors. When APCs were infected with a rVV encoding both MART-1/Melan-A27-35 and B7-1/2 (rVV-B7.1/2-M), a significantly more effective CTL generation was observed as compared with cultures stimulated by APCs infected with a rVV encoding the TAA epitope only (rVV-M). These enhancing effects were detectable irrespective of a previous VV-specific sensitization. Most importantly, fibroblasts, devoid of antigen-presenting capacity upon peptide pulsing or infection with rVV-M, could be turned into effective APCs after infection by rVV encoding TAA epitopes and costimulatory molecules. In these experiments, by using separate recombinant viral constructs, we observed a predominant role of B7-1 as compared with B7-2 in the induction of TAA-specific CTLs. Taken together, our data indicate that replication-incompetent rVV encoding TAA epitopes and costimulatory molecules are able to induce highly effective generation of tumor-specific CTLs. Therefore, these vectors could represent valuable clinical tools for immunotherapy of melanoma patients.

Antigen-Presenting Cells

Consumption of fatty fish from the Baltic Sea and PCB in whole venous blood, plasma and cord blood from delivering women in the Aland/Turku archipelago.

The present study aimed to assess the role of fish consumption for the body burden of polychlorinated biphenyls (PCBs) in mothers living in the Aland and Turku archipelago in Finland. The overall objective was to investigate whether there exists an appropriate population for a full-scale prospective study on PCB-related developmental effects in infants. Concentrations of the four major PCBs were determined in whole venous blood and cord blood from 30 delivering mothers, of which 20 subjects consumed fatty fish from the Baltic Sea (2.5-12.5 meals per month) and the remaining 10 mothers did not. The concentrations of CB-118, CB-138, CB-153, and CB-180 in cord blood were generally two- to threefold lower than in whole blood from the mothers, but strong correlations were observed between PCBs in the two matrices (r = .67-.80). Neither the venous blood nor cord blood concentrations of PCBs, however, were correlated with stated fish intake. Moreover, the concentration of CB-153 in plasma was only weakly associated with fish intake, and the level of organic mercury in erythrocytes was not correlated with fish intake at all. The present results of CB-153 concentrations in women's blood are lower than those reported in other recent investigations. A reasonable contributing explanation is the rapid decline during the last decades of PCB in Baltic Sea fish, which has resulted in less impact of fish intake on the body burdens of PCB in relatively young women (median 30 yr in the present study) as compared with older females. The relatively low PCB levels in blood taken together with the low number of yearly deliveries in the archipelago population makes it an inappropriate study base for a prospective study of PCB-related health effects in infants.

Adult

C-type lectin-like receptors in peptide-specific HLA class I-restricted cytotoxic T lymphocytes: differential expression and modulation of effector functions in clones sharing identical TCR structure and epitope specificity.

C-type lectin-like inhibitory receptors are heterodimers consisting of CD94 and NKG2-A-B molecules expressed on NK cells and on a subset of activated T lymphocytes. Their inhibitory effects on NK cytotoxicity and on the NK-like activity of T cell clones have been demonstrated, but no data are currently available on antigen-specific class I-restricted cytotoxic T lymphocytes (CTL). We have generated a panel of HLA-A2.1-restricted CTL clones directed against a nonapeptide derived from a melanoma-associated antigen, dopachrome tautomerase (TRP-2). All clones were CD8+ and TCR alphabeta+. About half of them expressed a CD94bright phenotype, whereas the remaining were CD94dim. Only the CD94bright CTL expressed the NKG2-A-B gene, consistent with the expression of a C-type, lectin-like, inhibitory CD94/NKG2-A-B heterodimer. Both CD94bright and CD94dim clones appeared to require similar amounts of synthetic epitope sensitizing target cells. Addition of anti-CD94 mAb resulted in a significant increase of specific killing by CD94bright, but not by CD94dim clones in the presence of suboptimal concentrations of peptide, whereas, when optimal amounts were used, the mAb did not induce a significant modulation of the cytotoxicity. Antigen-induced inward [Ca2+]i fluxes were unaffected, but an enhancement of TCR down-modulation could be observed in the presence of anti-CD94 mAb at high concentration of antigenic peptide. The analysis of the TCR-Vbeta repertoire of the CTL clones by RT-PCR and immunofluorescence revealed that all clones regardless of CD94 phenotype shared Vbeta22 expression. Most importantly, sequence analysis showed that they all expressed identical Vbeta22 TCR rearranged with Jbeta2.1 and Cbeta2. Taken together, these data indicate that different expression of functionally active lectin-like inhibitory receptors can be detected in CTL clones sharing identical TCR sequence and peptide specificity.

Amino Acid Sequence