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Background and study aims : To investigate the safety and efficacy of splenectomy for hepatolenticular degeneration (HLD) patients with PLT less than 20 × 109/L. Patients and methods : A total of 244 HLD patients with hyper-splenism underwent splenectomy. According to the preopera-tive PLT values, the patients were divided into three groups : group A of 53 patients with PLT < 20 × 109/L ; group B of 92 patients with 20 × 109/L ≤ PLT ≤ 30 × 109/L ; group C of 99 patients with PLT > 30 × 109/L. General information including : blood cell counts, liver function , coagulation function 1 day before sugery and 1, 7, 14 days after surgery ; intraoperative blood loss ; operation time ; vital signs at the beginning, at 60 minutes and the end of the operation. Pressure and blood oxygen ; postoperative drainage ; postoperative complications and mortality. Results : Blood cell counts, liver function, and coagulation func-tion were improved after splenectomy in three groups (P0.05). Conclusion : For HLD patients with hypersplenism, it is safe and effective to conduct splenectomy under PLT < 20 × 109/L.

Fall is the major risk factor of fracture that has not been included in FRAX®. Whether different age may determine the effect of falls on FRAX® is still uncertain. This epidemiological cohort study reveals that history of fall is a significant predictor of incident fracture independent of FRAX probability, especially in subjects

BACKGROUND Osteoporosis is a global disease burden for aging society. The role of quantitative ultrasound (QUS) in the prediction for osteoporosis in a dose-response manner is hardly addressed. AIM We aimed to show the dose-response of QUS measurement in the prediction for osteoporosis by a community-based study. DESIGN A prospective cohort study. METHODS Participants were recruited between 2000 and 2004. Demographic data and heel QUS measurement were collected at baseline. Diagnosis of osteoporosis was ascertained by the follow-up of this cohort over time. In order to reduce the imbalance of baseline characteristics in the observational study, we applied propensity score by using proportional odds regression analysis to match the quintiles of QUS T-score. RESULTS A total of 44 957 subjects composed of 17 678 men (39.3%) and 27 279 women (69.7%) were recruited. After adjustments for propensity score, an increase in one unit of QUB T-score led to 7% reduction in the risk for osteoporosis [adjusted odds ratio (OR) = 0.93, 95% confidence interval (CI): 0.89-0.96, P

Objective: To investigate the plasma osteoprotegerin level and osteoprotegerin expression in renal biopsy tissue in type 2 diabetes with nephropathy. Methods: Plasma osteoprotegerin level was measured by enzyme-linked immunoassay in 48 type 2 diabetes with normoalbuminuria, 48 patients with microalbuminuria, 44 patients with macroalbuminuria and 40 healthy persons. Part of diabetes patients with nephropathy were performed kidney biopsy by ultrasound guide. The osteoprotegerin expression in kidney biopsy tissue is examined by immunohistochemistry. Results: The plasma osteoprotegerin levels were significantly elevated in patients with microalbuminuria (3.73±0.75 ng/l) and macroalbuminuria (4.68±0.82 ng/l) as compared with patients with normoalbuminuria (2.71±0.69 ng/l) and control subjects (2.11±0.42 ng/l). And the plasma osteoprotegerin level in macroalbuminuric group was also higher than that in microalbuminuria group. The plasma osteoprotegerin level had a positive correlation with the fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), glycohemoglobinA1c (HbA1C), high sensitive C-reactive protein (hsCRP) and log(UAER). Multivariate regression analysis revealed that plasma osteoprotegerin level was an independent factor associated with albuminuria in type 2 diabetes. The immunohistochemistry results showed that positive immunostaining for osteoprotegerin was observed in the renal tubule cells of biopsy and not in glomerulus, and the osteoprotegerin expression was higher in macroalbuminuria group than that in microalbuminuria group. Conclusions: The plasma osteoprotegerin level and the osteoprotegerin expression in renal tubule cells of biopsy tissue were increased in nephropathy of type 2 diabetes. This finding supports the growing concept that osteoprotegerin may act as an important regulatory molecule in the angiopathy, and particularly, that it may be involved in the occurrence and development of nephropathy in type 2 diabetes.

This report describes the analytical validation and application of the homogeneous mobility shift assay (HMSA) method for the measurement of adalimumab and human antibodies-to-adalimumab (ATA) in serum samples from patients who have lost response to adalimumab treatment. Validation of the ATA- and the adalimumab-HMSA revealed a lower limit of detection to be 0.026U/mL for ATA and 0.018μg/mL for adalimumab in serum samples. Intra-assay and inter-assay precision determination yielded a coefficient of variation of less than 15%, and the accuracy of both assays was within 20%. Adalimumab drug tolerance in the ATA-HMSA was up to 20μg/mL in the test serum. Serum samples from 100 drug-naïve healthy subjects were tested to set-up the cut point of 0.55U/mL for ATA and 0.68μg/mL for adalimumab. Analysis of 100 serum samples from patients who were losing response to adalimumab showed that 26% had an adalimumab level below the cut point, of these 68% were ATA positive. Overall, 44% of the patients (44/100) were positive for ATA. This study presents evidence that drug and anti-drug antibody levels are important determinants of patient response to therapy.

Antibody-based drugs such as infliximab (IFX) are effective for the treatment of inflammatory bowel disease (IBD) and other immune-mediated disorders. The development of antibodies against these drugs may result in unfavorable consequences, including the loss of drug efficacy, hypersensitivity reactions, and other adverse events. Therefore, accurate monitoring of serum drug and anti-drug antibody levels should be an important part of therapy for patients being treated with an antibody-based drug. Current methods for the assessment of anti-drug antibodies and drug levels, involving various bridging ELISA and radioimmunoassay techniques, are limited by their sensitivity, interference, and/or complexity. To overcome these limitations, we have developed a non-radiolabeled homogeneous mobility shift assay (HMSA) to measure the antibodies-to-infliximab (ATI) and IFX levels in serum samples. Full method validation was performed on both the ATI- and IFX-HMSA, and the clinical sample test results were also compared with those obtained from a bridging ELISA method to evaluate the difference in performance between the two assays. Validation of the ATI-HMSA revealed a lower limit of quantitation of 0.012μg/mL in serum. The linear range of quantitation was 0.029–0.54μg/mL. The intra- and inter-assay precision was less than 20% of coefficient of variation (CV), and the accuracy (% error) of the assay was less than 20%. In serum samples, ATI as low as 0.036μg/mL can be measured, even in the presence of 60μg/mL of IFX in the serum. Sera from 100 healthy subjects were tested to determine the cut point of the assay. ATI-positive samples that had been previously analyzed by using a bridging ELISA from 100 patients were also measured by the new method. There was a high correlation between the two methods for ATI levels (p

Background The amyloid neuritic plaque is considered to be a toxic collection of amyloid-s protein found in brain tissue in Alzheimer's disease. A neutral analogue of the amyloid-binding thioflavin-T (BTA), has been radiolabeled as [C-11]-6-OH-BTA-1. It crosses the blood brain barrier, and is a promising tracer for imaging plaques in vivo using positron emission tomography. We now report the biodistribution and dosimetry of [C-11]-6-OH-BTA-1 in baboons. Methods Four 2-hour whole body studies were acquired in an ECAT ACCEL camera in two baboons after the bolus injection of [C-11]-6-OH-BTA-1. After 3.5 minute transmission scans performed per bed position prior to injection, emission scans were collected in 2-D mode over five bed positions. Regions of interest (ROI) were drawn around the brain, left and right lungs, heart, liver, gall bladder, left and right kidneys, spleen and urinary bladder. Since no fluid was removed from the baboons, total body radioactivity was calculated using the injected dose and a calibration factor determined from a cylinder phantom. The area under the curve (AUC) for each ROI was determined by trapezoidal integration of the first few points with subsequent points fit by a decreasing monoexponential. The AUC was then divided by counts in the total body, and resulting residence times were entered into the MIRDOSE3 program. Results The animals tolerated the procedure well. The ligand was eliminated via the hepatobiliary and renal systems. In the adult male and female reference the gallbladder received the highest estimated radiation dose and was the critical organ (3.9E–02 mGy/MBq and 4.3E–02 mGy/MBq respectively). Conclusion In the United States, the absorbed dose to the gallbladder would limit [C-11]-6-OH-BTA-1 administered with the approval of a Radioactive Drug Research Committee (RDRC) to a single injection of 1295 MBq (35 mCi) in the adult male, and 1314 MBq (35 mCi) in the adult female.

Binding competition between endogenous dopamine (DA) and the D2 receptor radiotracer [123I]IBZM allows measurement of the change in synaptic DA following amphetamine challenge with SPECT in the living human brain. Previous investigations using this technique in healthy subjects have shown that the magnitude of amphetamine effect on [123I]IBZM binding potential (BP) is small (range between 5 to 15% decrease), and that a large between-subject variability in this effect is observed. Therefore, it was unclear how much of the apparent between-subject variability was due to a low signal-to-noise ratio in the measurement, vs. true between-subject differences in the magnitude of the response. The goals of this investigation were to test the within-subject reproducibility and reliability of amphetamine-induced decrease in [123I]IBZM BP with a test/retest paradigm, and to establish the presence or absence of tolerance or sensitization to single administration ofi.v. amphetamine. Six healthy male subjects, never previously exposed to psychostimulants, twice underwent measurement of striatal amphetamine-induced DA release (between-measurement interval 16 +/- 10 days) using SPECT and the [123I]IBZM constant infusion technique. Results demonstrated an excellent within-subject reproducibility of amphetamine-induced DA release: amphetamine-induced decreases in [123I]IBZM BP were significant on each day, and had an intraclass correlation coefficient (ICC) of 0.89. Moreover, values from the second experiment were not significantly different from first experiment, suggesting the absence of either sensitization or tolerance to the effect of amphetamine on DA release in these experimental conditions. The subjective activation, as rated by the subjects on analog scales, was also highly reproducible. In conclusion, this scanning technique provides a reliable measurement of amphetamine-induced reduction of [123I]IBZM BP and enables detection of between-subject differences that appear stable over time.

LY274601, R-(+)-8-thiomethyl-2-(di-n-propylamino)tetralin, a serotonin (5-HT) 1A receptor full agonist with high affinity (Ki: 0.6nM) and selectivity, was labeled with 11 C for imaging 5-HT 1A receptor sites in vivo by positron emission tomography (PET). [ 11 C]LY274601 was synthesized by S-methylation of the normethyl precursor unmasked via hydrolysis of the butyrate thioester of LY274601. The methylation reaction with [ 11 C]iodomethane proceeded quickly and efficiently in DMF at 40°C, yielding the radiotracer in an average overall radiochemical yield of 35.7±9.8%, The synthesis time including HPLC purification and formulation for injection was approximately 30 min. The specific activity was 630±78mCi/μmol at the end of synthesis (E.O.S.). This labeling procedure was also employed in the preparation of [ 3 H]LY274601, R-(+)-8-[ 3 H]methylthio-2-(di-n-propyl-amino)tetralin, from [ 3 H]iodomethane.

Background Because streptavidin shows high localization in inflamed tissues, it might also interfere with the proliferation of cells involved in allograft rejection. Methods and results Treatment of naive ACI recipients with 20 mg/kg streptavidin i.p. alone significantly prolonged Lewis cardiac allografts from a mean survival time of 9.8+/-0.7 days in controls to 19.8+/-6.5 days, with one recipient accepting the graft permanently (>250 days). Peritransplant streptavidin treatment combined with 0.5 ml of antilymphocyte serum (ALS) transient immunosuppression led to permanent graft survival (>250 days) in 6 of 10 recipients. Second-set skin grafts performed 60 days after the primary cardiac allograft were prolonged to 45 days, whereas the third party Wistar-Furth (WF) skin grafts were rejected in 15 days without the rejection of the primary Lewis cardiac allografts. Pathology of transplanted cardiac allografts at 100 days showed no mononuclear cell infiltration or chronic allograft vasculopathy. Streptavidin given for 5 days at 20 mg/kg caused a moderate initial weight loss but had no effect on hematologic, biochemical, and histologic parameters in the treated recipients. Conclusion This study demonstrates that peritransplant recipient treatment with streptavidin combined with peritransplant ALS induces prolonged cardiac and second-set skin allograft survival. We conclude that recipient peritransplant streptavidin treatment may provide a new strategy for the induction of transplant tolerance.

The human high-molecular-weight melanoma-associated antigen (HMW-MAA) represents a useful marker for immunoscintigraphy in patients with melanoma. Since injection of a radiolabelled anti-HMW-MAA monoclonal antibody (MAb) visualizes only about 60% of melanoma lesions, approaches are being developed to increase the sensitivity of immunoscintigraphy. One of them aims at improving the immunoreactivity of radiolabelled anti-HMW-MAA MAbs, since this approach may improve the targeting of radiolabelled MAbs to melanoma lesions. We have previously shown that affinity chromatography on insolubilized anti-idiotypic MAbs is a useful method for purifying immunoreactive anti-HMW-MAA MAb TP61.5 from 125I-labelled MAb preparations and that not all the anti-idiotypic MAbs are useful for this purpose. Since the increasing number of available anti-idiotypic MAbs is likely to facilitate the application of this procedure in many antigenic systems, we have now tested criteria to select anti-idiotypic MAbs suitable for the purification procedure. Furthermore, we have investigated the effect of the increase in immunoreactivity of 125I-MAb TP61.5 on its in vivo targeting to human melanoma lesions transplanted into nude mice. Among the 3 anti-idiotypic MAbs tested, the most effective in purifying immunoreactive MAb TP61.5 molecules following radiolabelling is MAb TK7-110, with which 125I-MAb TP61.5 displays an immunoreactivity similar to that displayed with melanoma cells. This parameter may represent a useful criterion to identify anti-idiotypic MAbs suitable for the purification procedure, if the present results are confirmed with a large number of anti-idiotypic MAbs in different antigenic systems. We have also shown that an incubation time for up to 4 hr of 125I-MAb TP61.5 with insolubilized MAb TK7-110 is the most effective in increasing immunoreactivity and in recovering immunoreactive MAb applied to the affinity matrix. The increase in the immunoreactive fraction of 125I-MAb TP61.5 significantly increases its specific localization in human melanoma lesions transplanted into nude mice. These results suggest that purification of radiolabelled immunoreactive anti-HMW-MAA MAb TP61.5 by affinity chromatography using anti-idiotypic MAb TK7-110 represents a useful approach to increasing the sensitivity of immunoscintigraphy in patients with melanoma.

Objective The serotonin transporter has been implicated in a variety of conditions including mood disorders and suicidal behavior. In vivo human brain studies with positron emission tomography and the serotonin transporter antagonist [ 11 C]DASB ([ 11 C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) are ongoing in several laboratories with the maximum administered activity based on dosimetry collected in rodents. We report on the biodistribution and dosimetry of [ 11 C]DASB in the baboon as this species may be a more reliable surrogate for human dosimetry. Methods Four baboon studies (two studies in each of two baboons) were acquired in an ECAT ACCEL camera after the bolus injection of 183±5 MBq/2.3±1.0 nmol of [ 11 C]DASB. For each study, six whole-body emission scans were collected in 3D mode over 6/7 bed positions for 2 h. Regions of interest were drawn on brain, lungs, liver, gallbladder, spleen, kidneys, small intestine and bladder. Since no fluid was removed from the animal, total body radioactivity was calculated using the injected dose calibrated to the ACCEL image units. Results Uptake was greatest in lungs, followed by the urinary bladder, gallbladder, brain and other organs. The ligand was eliminated via the hepato-billiary and renal systems. The largest absorbed dose was found in the lungs (3.6×10 −2 mSv/MBq). The absorbed radiation doses in lungs and gallbladder were four and nine times larger than that previously estimated from rat studies. Conclusion Based on our baboon biodistribution and dose estimates, the lungs are the critical organs for administration of [ 11 C]DASB. In the United States, the absorbed dose to the lungs would limit [ 11 C]DASB administered with the approval of a Radioactive Drug Research Committee to 1400 MBq (37 mCi) in the adult male and 1100 MBq (30 mCi) in the adult female.

UNLABELLED Intracarotid infusion of short-acting vasodilators, such as adenosine and nitroprusside, in doses that lack significant systemic side effects, may permit controlled manipulation of cerebrovascular resistance. In this experiment we assessed changes in cerebral blood flow (CBF) after intracarotid infusion of nitroprusside and adenosine. The study was conducted on six adult baboons under isoflurane anesthesia and controlled ventilation. Intracarotid drug infusion protocol avoided hypotension during nitroprusside infusion and tested for autoregulatory vasoconstriction. CBF (intraarterial (133)Xe technique) was measured four times during infusions of 1) intracarotid saline, 2) IV phenylephrine (0.2 microg x kg(-1) x min(-1)) aimed to increase mean arterial pressure by 10-15 mm Hg, 3) IV phenylephrine and intracarotid nitroprusside (0.5 microg x kg(-1) x min(-1)), and 4) intracarotid adenosine (1 mg/min). IV phenylephrine increased mean arterial pressure (69 +/- 8 to 91 +/- 9 mm Hg, P < 0.0001, n = 6), and concurrent infusion of intracarotid nitroprusside reversed this effect. However, compared with baseline, CBF did not change with IV phenylephrine or with concurrent infusion of IV phenylephrine and intracarotid nitroprusside. Intracarotid adenosine profoundly increased CBF (from 29 +/- 8 to 75 +/- 32 mL x 100 g(-1) x min(-1); P < 0.0001). In nonhuman primates, intracarotid adenosine increases CBF in doses that lack significant systemic side effects, whereas intracarotid nitroprusside has no effect. Intracarotid adenosine may be useful for manipulating cerebrovascular resistance and augmenting CBF during cerebral ischemia. IMPLICATIONS Intraarterial (133)Xe cerebral blood flow (CBF) measurements suggest that intracarotid adenosine, in a dose that lacks significant systemic side effects, profoundly increases CBF, whereas nitroprusside has no effect.(5-12)

LY274601 [R-(+)8-thiomethyl-2-(di-n-propyl-amino)tetralin], a full agonist of the 5-HT1A receptor with high affinity and selectivity, was labeled with 11C and 3H, and its in vivo behavior was studied to evaluate [11C]LY274601 as a PET radiotracer for imaging 5-HT1A receptor sites in living brain. Following intravenous tail injection into mice, [11C]LY274601 showed high blood-brain barrier permeability and accumulated in regions known to have high densities of 5-HT1A receptor sites such as the brain stem including the raphe nuclei. The binding of the radiotracer in target tissues is blocked by pre-injection of the 5-HT1A receptor selective ligand 8-OH-DPAT (1 mg kg , sc), suggesting that the binding is specific to 5-HT1A receptor sites. Using ex vivo autoradiography, the target tissues such as hippocamous CA1-4 fields, piriform cortex, dorsal raphe nucleus and lateral septum were visualized as hot spots. These tissues were observed to have binding 2–2.7 times greater than the cerebellum. The distribution of the radiotracer agrees well with the distribution of 5-HT1A receptors revealed by in vitro autoradiography with [3H]8-OH-DPAT. However, the radiotracer was metabolized quickly and cleared from target tissues with a half life of approximately 15 min. [11C]LY274601 showed high non-specific binding in regions with low number of 5-HT1A receptor sites such as cerebellum.

The assessment of the effects of covariates or potential risk factors on the times to events in a complex longitudinal study is an important problem in survival analysis. In such studies, individuals often enter at different ages and the particular endpoint of interest may or may not be observed during the study period. Such event times are right censored. Most statistical methods deal with this problem when the individual event times are statistically independent. In many studies, such as the Framingham Heart Study, event times between different endpoints on the same individual or between groups of individuals may be associated. For example, event times within individuals (e.g., age at first evidence of hypertension, glucose intolerance, coronary heart disease, cardiovascular disease) may be associated. Also, it is reasonable to presume that individuals in the same household, such as husbands and wives who share common unmeasured environmental hazards (diet, radon levels, etc.), or, siblings who share common genetic factors, will have associated times to occurrence of certain diseases or to death. We model such potential dependencies by the introduction of a “frailty” into the model that represents shared unobservable genetic or environmental random effects.

To further define the underlying mechanisms of immune suppression induced by UV-B irradiation, we have examined the kinetics of homing patterns of in vitro UV-B-irradiated and gamma-irradiated-thoracic duct lymphocytes (TDL) compared to dendritic cells (DC). Our findings show that 111In-oxine-labeled TDL specifically home to the spleen, liver, lymph nodes, and bone marrow with subsequent recirculation of a large number of cells from the spleen to lymph nodes. In contrast, DC preferentially migrate to the spleen and liver with a relatively insignificant distribution to lymph nodes and an absence of subsequent recirculation. Splenectomy prior to cell injection significantly diverts the spleen-seeking DC to the liver but not to the lymph nodes, while the homing of TDL to lymph nodes is significantly increased. In vitro exposure of 111In-oxine labeled TDL to gamma irradiation does not significantly impair immediate homing to lymphoid tissues but inhibits cell recirculation between 3 and 24 hr. In contrast, gamma irradiation does not affect the tissue distribution of labeled DC, suggesting that DC are more radioresistant to gamma irradiation than TDL. Unlike the findings in animals injected with gamma-irradiated cells, UV-B irradiation virtually abolished the homing of TDL to lymph nodes and significantly reduced the homing of the spleen-seeking DC to the splenic compartment while a large number of cells were sequestered in the liver. The results of in vitro cell binding assay show that TDL, unlike DC, have the capacity to bind to high endothelial venules (HEV) within lymph node frozen sections while gamma and UV-B irradiation significantly inhibit the binding of TDL to lymph node HEV. These findings suggest that: (i) DC, unlike TDL, are unable to recirculate from blood to lymph nodes through HEV; (ii) although gamma irradiation impairs TDL recirculation, it does not affect DC tissue distribution; and (iii) UV-B irradiation impairs both TDL and DC migration patterns. We conclude that the lack of capacity of irradiated TDL to home to lymph nodes is due to damage to cell surface homing receptors and that the failure of DC to home to the lymph node microenvironment is related to the absence of HEV homing receptors on their cell surface.

Four steps were required to synthesize the title compound. This involved carboxylation, acid chloride formation, condensation, and hydrazone formation. The overall radiochemical yield was 12.5% amd the specific activity was 2.04 mCi/mmole. Because of the difficulty encountered in preparing the p-fluorobenzal-dehyde-aldehyde-14C, p-fluorobenzoyl chloride-carbonyl14C was used for the condensation reaction.

Factors that might affect the biodistribution and clinical utility of radiolabeled lymphocytes were evaluated in experimental animals. Indium-111 (In-111) labeled lymphocytes (10(7)-10(9) syngeneic or allogeneic cells; 1-10 microCi [.037-.37 MBq]/10(8) cells) obtained from peripheral blood, lymph node, or spleen were found in significant amounts in the lymphoid tissues of Lewis rats as early as 3 hours after infusion. A progressive increase in nodal activity with concomitant fall of activity in other organs followed, indicating active recirculation of the lymphocytes. However, In-111 labeled thymocytes or xenogeneic lymphocytes failed to accumulate in lymphoid tissue. In vitro irradiation of the In-111 labeled lymphocytes (100-400 rads [1-4 Gy]) before in vivo administration and increase of the In-111 to 40 microCi [1.48 MBq]/10(8) lymphocytes resulted in no detectable lymphocyte recirculation and/or reduced localization in lymphoid tissue. Splenectomized animals and those sensitized to an organ allograft before cell infusion showed increased activity in their bone marrow. These results suggest that the source of the injected cells, cell irradiation dose level, and host sensitization should be considered when radiolabeled lymphocytes are being prepared for use in clinical diagnosis and therapy.

The biodistribution of radiolabeled mouse anti-pan T monoclonal antibody (W3/13) against rat lymphocytes was examined in normal rats. Monoclonal antibody to human prostate-associated antigens (PAA) served as a control. In vitro studies demonstrated a 38% maximum binding of radiolabeled W3/13 to lymphocytes, which was significant (P less than 0.001) when compared with the control (PAA) value of 3.4%. In vivo, intravenously administered 111In labeled W3/13 and 131I labeled W3/13 exhibited similar tissue distribution patterns. The localization of W3/13 in lymphoid tissue was significantly greater than that achieved with PAA. W3/13, however, did not demonstrate significant localization in the intact thymus and accumulated to a higher degree (6-10% ID/g) than expected in bone marrow at 24 h. These findings suggest that radiolabeled anti-lymphocyte monoclonal antibodies may not be well suited for the treatment of lymphoreticular neoplasms and allograft rejection in patients.

This study examined the feasibility of rapid rCBF monitoring using 133Xe as a tracer during operative procedures. We compared the initial slope index derived from two bicompartmental and one monocompartmental physiological models. The single-compartment model requires only 3 min of monitoring, whereas the bicompartmental models, thought to be more reliable, require 11 min of clearance. Data were collected from 26 patients undergoing carotid endarterectomy. Approximately 20 mCi of 133Xe in saline was injected i.v. for up to five measurements per patient, for a total of 117 measurements. The robustness of the regression for the three parameters ( r = 0.781–0.99, p < 0.0001) suggests that the three parameters are closely related. This is supported by similarity of the slopes of the regression lines (between 0.944 and 1.25) and the mean ± SD of the three rCBF models (24.9–27.5 ± 12.0–14.3 ml 100 g−1 min−1). Similar results were obtained for individual detectors, despite the expected higher variability. For intraoperative use in surgical procedures in which physiological conditions may change rapidly and i. v. injections of tracer must be used, a rCBF index that quickly and accurately reflects flow conditions is useful. Our data suggest that the single-compartmental Wyper index may be used to provide information about cerebral perfusion that is as accurate and robust as bicompartmental models, but requires only one-quarter of the data collection time.

The bicyclic anhydride of DTPA-1- 14 C (BADTPA-1- 14 C) was synthesized and reacted with an antibody to human melanoma associated antigen (MAA) and with one to human class II major histocompatibility complex antigen (HLA-DR). DTPA-1-C incorporation per mole of anti MAA at molar ratios of 1:1 to 200:1 ranged from 0.5 to 25, while immunoreactivity ranged from 49 to 9%. With antibody to HLA-DR, results were similar. Anti MAA, but not anti HLA-DR, demonstrated polymerization upon conjugation. BADTPA-1- 14 C provides a convenient and accurate method for measuring the amount of DTPA in monclonal antibody preparations and its effect on immunoreactivity.

SummaryThe biodistribution of lymphocytes labeled with 109Pd was investigated in Lewis rats to determine if they might be useful for selective lymphoid ablation. 109Pd-labeled lymphocytes demonstrated significant lymphoid localization. However, there was a fall in the accumulation of radiolabeled lymphocytes in lymphoid tissue when the 108Pd carrier dose or the 109Pd radioactive dose incorporated per 108 lymphocytes was increased from 0.12 mg to 0.20 mg and from 21.3 µCi to 54.6 µCi, respectively (P

The present experiment was designed to study the relationship between rat heart allograft survival and passenger leukocyte depletion in donor-pretreated animals. Untreated Lewis rats served as recipients of cardiac allografts from treated Fischer rats. Passenger leukocyte depletion was assayed with indium-111 oxine-labeled leukocytes (predominantly lymphocytes) which were infused into donor rats 6 hr before treatment with cyclophosphamide, antilymphocyte globulin (ALG), sublethal total body irradiation, or in vitro perfusion-preservation of the isolated beating heart. In vivo pretreatment of the donor with cyclophosphamide resulted in a significant prolongation of heart allograft survival but effected no reduction in graft-labeled lymphocytes. In vitro perfusion-preservation of the donor heart, for 1 to 2 hr, led to a 50 to 60% reduction in graft-labeled lymphocytes but failed to significantly prolong the survival of the heart allografts. Both ALG and sublethal total body irradiation donor pretreatments resulted in significant prolongation of heart allograft survival and a 20 to 25% labeled passenger lymphocyte depletion. This study demonstrates that there is no direct correlation between allograft survival and the degree of mobile passenger lymphocyte depletion, suggesting that the efficacy of leukocytotoxic donor pretreatment methods may depend in part on alternative mechanisms.

SummaryThe cyclic anhydride (CA) and the mixed anhydride (MA) of DTPA were synthesized and used to chelate 111In to an antimelanoma monoclonal antibody. The CA and MA methods showed mean labeling efficiencies of 25.7 and 20.5%, respectively (p = NS). The binding efficiency of labeled antibody to human melanoma cells in tissue culture also was similar (x̄ = 52 and 50%, respectively, p = NS), as was tumor uptake in nude mice at 96 hrs post-injection (16%-CA vs 12%-MA). The method required less complicated chemical syntheses, much less preparation time, and the product was stable over a much longer period. The results suggest that the CA method is preferable for bifunctional chelate labeling of monoclonal antibodies with 111In-DTPA.

This study evaluates the kinetics and utility of infused indium-111-labeled cells in detecting rejection in ACI to Lewis rat heart allografts. Syngeneic leukocytes, lymph node lymphocytes, and platelets were isolated and labeled with indium-111 (/sup 111/In) oxine, respectively, and were infused i.v. into Lewis rats carrying beating ACI or syngeneic hearts from post-transplant days 0 to 6. Recipients were imaged serially at 24 hr after infusion of labeled cells followed by excision of both native and transplanted hearts for direct isotope count. Labeled leukocytes accumulative progressively in the allograft with the scan becoming positive by post-transplant day 4. The ratio of allograft to native heart isotope counts rose from 1.25 on day 1 to 10.07 (P less than 0.0001) on day 7. The Lewis recipients infused with labeled lymphocytes showed a positive scan on days 6 and 7 whereas the allograft to native heart isotope count ratio rose from 0.97 on day 1 to 5.33 (P less than 0.001) on day 7. Recipients infused with /sup 111/In-labeled platelets showed a positive scan on days 5 to 7 and the allograft to native heart isotope count ratio rose sharply from 2.56 on day 4 to 16.98 (P less than 0.005) onmore » day 7. Syngeneic heart grafts failed to demonstrate significant accumulation of any of the labeled cell population. These studies confirm the importance of nonlymphocytic cells in cellular rejection, evaluate the kinetics of graft invasion by the various cell types, and suggest that the techniques used afford a method for a safe and an early detection of allograft rejection.« less

Recent advances in hybridoma technology have led to the development of specific monoclonal antibodies to a variety of tumor-associated antigens. The high degree of specificity of such reagents has rekindled interest in their application to immunotherapy of malignancies. In-vitro culture studies and experiments in various in-vivo animal models have usually shown that monoclonal antibodies, even in the presence of complement, are rarely alone sufficiently cytotoxic and therefore usually ineffective for tumor destruction (1,2). This ineffectiveness of monoclonal antibodies when used in unmodified forms has been partially attributed to the heterologous distribution of tumor-associated antigens on tumor cell surfaces which therefore results in an insufficient attachment of monoclonal antibodies to different tumor cells; more to those cells which have a significant number of binding sites for the antigen but none to other tumor cells that are devoid of binding sites for the specific antigen (3). Thus, while tumor cells which express the specific antigen may under appropriate circumstances undergo lysis, those which are negative for the antigen are spared and continue to proliferate. Monoclonal antibodies directed to tumor-associated antigens which are coupled to various toxins suffer from the same shortcomings that have been described for unmodified antitumor monoclonal antibodies.

Pure and doped single crystals of hematite were investigated using microwave techniques. Our results show that both the field required for resonance and the linewidth increase with Ti doping, and that the linewidth of the Ti‐doped samples favors a slow relaxation process. It is found that values of HD′, the canting field determined by resonance, and HD, the static canting field are related by HD′=HD+4HMHK0′/HD. However, Ti‐doped samples must be treated by considering a three‐sublattice model.