Characterization of N-cadherin unbinding properties in non-malignant (HCV29) and malignant (T24) bladder cells

The expression of N‐cadherin, characteristic of various cancers, very often leads to changes in the cells' adhesive properties. Thus, we sought to find out if N‐cadherin expressed in various, but cancer‐related cells, differs in its functional properties that could contribute to variations in cells' phenotypes. In our work, measurements of an unbinding force of a single N‐cadherin molecule, probed with the same antibody both on a surface of living non‐malignant (HCV29) and malignant cells (T24) of bladder cancer, were carried out with the use of an atomic force microscopy. The results show the enhanced N‐cadherin level in T24 malignant cells (8.7% vs. 3.6% obtained for non‐malignant one), confirmed by the Western blot and the immunohistochemical staining. The effect was accompanied by changes in unbinding properties of an individual N‐cadherin molecule. Lower unbinding force values (26.1 ± 7.1 pN) in non‐malignant cells reveal less stable N‐cadherin complexes, as compared to malignant cells (61.7 ± 14.6 pN). This suggests the cancer‐related changes in a structure of the binding site of the antibody, located at the extracellular domain of N‐cadherin. Copyright © 2011 John Wiley & Sons, Ltd.     

Malignant Glial Neoplasms: Definition of a Humoral Host Response to Tumor-Associated Antigen(s)

There is increasing evidence that human tumors possess tumor-associated neo-antigens. The host mounts an immunological response to these antigens, as evidenced by the detection of circulating humoral antibodies in a variety of human neoplasia.An indirect immunofluorescent antibody technique was employed to detect antibodies to tumor-associated antigens in the sera of patients with malignant gliomas. Viable single cell suspensions were used to demonstrate antibodies to surface contents of tumor cells and cell preparations were snap-frozen at −160° C to demonstrate antibodies to cytoplasmic components of tumor cells. After incubation with serum, the preparations were treated with polyvalent sheep antihuman globulin conjugated to isomer-1-fluorescein isothiocyanate, washed, and examined with a Leitz incident fluorescent microscope.Of the 17 sera from histologically proven malignant glial neoplasm patients, 2 (11%) were positive for an autologous surface antibody reaction. Five (23%) of 21 were positive for an autologus cytoplasmic antibody, however, 10 (47%) of 21 of the sera gave a positive reaction for cross-reacting cytoplasmic antibodies when tested with a battery of tumor cells obtained from different patients with malignant glial tumors.No reaction was observed with normal brain tissue. Absorption studies indicated the presence of a tumor-associated antigen.This study demonstrated that certain patients with malignant gliomas possess circulating antibodies to cytoplasmic components of their own tumor cells. The fact that a number of sera cross-reacted with tumor cells obtained from different patients suggests that antigenic cross-reactivity exists between malignant glioma cells from different patients. It is suggested that with further refinement, immunofluorescent detection of antibodies could evolve as a useful diagnostic adjunct in malignant glioma.     

Cell kinetic analysis of mixed populations using three-color fluorescence flow cytometry.

The development of antibodies to DNA-incorporated thymidine analogs has in turn led to the development of flow cytometric techniques for rapidly measuring cell kinetics parameters. More recently, these techniques have been applied to clinical tumor material. One problem with such measurements has been the difficulty of distinguishing malignant cells from coexistent normal cells in the biopsy material. In the present study, the feasibility of selecting out the desired malignant cell population for kinetic analysis from a mixture of cells was tested in vitro. An anticytokeratin antibody was used to discriminate between a mixture of tumor cells (cytokeratin positive) and normal cells (cytokeratin negative). The cell lines chosen for the study, A549 human lung carcinoma cells and Chinese hamster ovary (CHO) cells, were pulse labeled with iododeoxyuridine (IdUrd) and sampled every hour up to 16 hours. Selecting out cells from the mixture required the application of three-color fluorescence flow cytometry, which was carried out using the fluorochromes FITC (fluorescein isothionate, green fluorescence, IdUrd-DNA antibody), PE (phycoerythrin, orange fluorescence, cytokeratin antibody), and PI (propidium iodide, red fluorescence, DNA). This allowed single laser excitation. The staining procedure involved incubation with the IdUrd antibodies (specific antibody plus FITC-conjugated second antibody) followed by the cytokeratin antibodies (specific antibody plus PE-conjugated second antibody) and lastly by the DNA stain containing RNase. Two analysis methods of the IdUrd/DNA cytograms were applied: a mid-S window analysis and a relative movement (RM) analysis. Results of the analyses for cells selected out of mixtures were compared with results of cells stained and analyzed separately. A clear separation of the two cell lines could be obtained on the basis of orange fluorescence (cytokeratin content) despite a large overlap of their DNA histograms. By gating on high or low orange fluorescence, almost pure populations of the individual cell types could be selected out for further kinetic analysis. Little difference was seen, with both the mid-S and RM analyses, between cells gated from mixtures or stained separately. It is concluded that this technique is feasible for use on clinical material, provided good cell suspensions can be obtained, leading to the hope of increasing the accuracy of kinetic measurements on human tumors.     

Heterologous anti-progesterone monoclonal antibody arrests early embryonic development and implantation in the ferret (Mustela putorius)

Early embryo development and implantation were arrested in ferrets passively immunized with a mouse monoclonal anti-progesterone antibody injected intraperitoneally at 72 and 96 h post coitum (p.c.) or at 72 h p.c. only. In control ferrets injected with mouse serum or 0.9% NaCl, implantation sites were found in all mated females; autopsies were carried out at Day 14 p.c. A total of 34 unimplanted embryos were recovered from the reproductive tract of antibody-treated ferrets and none of these had progressed to the blastocyst stage. When ferrets were treated with antibody at 72 h p.c. and autopsies were carried out at Day 6 p.c., only 1 of 29 embryos recovered had progressed beyond the 4-cell stage in 4 females. In 4 control animals most embryos recovered at Day 6 were at the morula (32%) or blastocyst (28%) stage. Embryos from ferrets treated with antibody were therefore developmentally arrested when recovered 72 h after antibody administration. Plasma progesterone concentrations were approximately 6-fold higher in antibody-treated ferrets with unimplanted embryos (711 +/- 132 nmol/l; 223 ng/ml) compared with control pregnant females (102 +/- 4 nmol/l; 32 ng/ml) at Day 14 p.c. The results are consistent with the hypothesis that the normal course of pregnancy is arrested as a result of antibody binding of progesterone in the circulation, presumably causing a decrease in the amount of progesterone available to target cell receptors, and that heterologous anti-progesterone antibody blocks normal cleavage and embryonic development at an early stage before cavitation.     

Diagnostic interest of the monoclonal antibody CA1 in malignant pleural effusion

The Ca1 antibody was used in an immunohistochemical procedure on smears of cells from 40 patients with malignant pleural effusion. The control group consisted of 25 benign pleural effusions with a high percentage of reactive mesothelial cells. The Ca1 Mc Ab was positive in 19 (79%) of the 24 pleural effusions with positive malignant cytology. In all the benign cases the Ca1 Mc Ab was negative (100% specificity). The Ca1 Mc Ab detected malignant mesothelial cells in two cases and was negative with reactive mesothelial cells and other nucleated cells present in the pleural effusion. We conclude that the Ca1 antibody offers a useful diagnostic method for malignant pleural effusions, when the morphological interpretation is doubtful.     

Diagnostic utility of sialosyl-Tn in discriminating carcinomatous cells from benign mesothelium in body cavity effusions

OBJECTIVE: Detecting malignant cells in the setting of reactive mesothelium can be difficult. Several techniques have been tried but without widespread acceptance. Sialosyl-Tn (STn) is an aberrantly glycosylated precursor of the MN blood group antigen frequently expressed in carcinomas and dysplastic epithelium. We investigated the STn monoclonal antibody for its clinical utility as an isolated stain to discriminate benign mesothelium from malignant cells. STUDY DESIGN: Cell block material from 72 cases of body cavity fluids were immunostained for STn using the avidin-biotin complex method without antigen retrieval. Slides were incubated overnight at 4 degrees C in a humidified chamber. RESULTS: Strong immunoreactivity was noted in 31/40 (77%) carcinomatous cases. Only moderate staining was noted in 1 of 28 (4%) benign effusions and weak staining in 5 (18%) additional benign cases. Specificity was 100%, sensitivity 78%, positive predictive value 100% and negative predictive value 76%. No staining was noted in four noncarcinomatous malignant effusions. CONCLUSION: STn may have diagnostic value in this cytologic setting as part of a diagnostic panel but not as an isolated stain.     

Diagnostic utility of BCA-225 in detecting adenocarcinoma in serous effusions

OBJECTIVE: To determine the diagnostic value of the BCA-225 antibody in discriminating adenocarcinoma from benign mesothelium in body cavity effusions. STUDY DESIGN: One hundred four cases of unequivocally benign (34 cases) and malignant (70 cases) serous effusions with cell block material were immunostained for BCA-225 using the ABC method without antigen retrieval. The percentage of positively staining cells in each case was estimated in a blind fashion. RESULTS: BCA-225 stained at least 10% of morphologically malignant cells in 28 of 32 (88%) breast carcinomas and 58 of 67 (87%) adenocarcinomas overall. Neuroendocrine carcinomas (two cases) and one mesothelioma were positive in < or = 5% of their respective tumor cells. Of 34 benign cases, 6 (18%) exhibited positive staining, albeit in rare, morphologically benign cells. CONCLUSION: BCA-225 is able to discriminate adenocarcinoma from reactive mesothelium in cell block preparations and may prove useful as part of an antibody panel.     

Human tumor and normal tissue reactivity of the anti-(breast cancer) monoclonal antibody BA-Br-3 and its similarity to the anti-(epithelial membrane antigen) monoclonal antibody E29

Summary A mouse monoclonal antibody (BA-Br-3) raised against the breast carcinoma cell line CAMA-1 was previously shown to react with a 300-kDa globule-like glycoprotein from human milk fat also expressed in the cytoplasm and on the surface of human carcinoma cells of different histological types. In this report the reactivity of this mAb with a large number of normal and malignant human tissues was analyzed using immunoperoxidase techniques. When tested on sections of both fresh-frozen tissues and formalin-fixed, paraffin-embedded tissues, BA-Br-3 reacted with a formalin-resistant antigenic determinant expressed by normal and malignant epithelial cells. Preferential reactivity was observed at the apical portion of ductal epithelial cells in normal breast and in glandular epithelia distributed in several other organs. Reactivity with mucin-like secretions in the lumina of ducts was also found. BA-Br-3 reacted mostly in heterogenous staining patterns with 88% of 49 breast carcinoma specimens tested, regardless of their histological type or whether they were primary or secondary neoplasms. Testing of epithelial malignant tumors other than breast carcinomas with this antibody showed that 127 of 151 (84%) were also reactive. mAb BA-Br-3 and E29 (a commercially available anti-(epithelial membrane antigen) shared very similar staining patterns and distributions of reactivity with breast and other epithelial tumors. However, BA-Br-3 showed a significantly higher percentage of reactivity with melanoma (33% versus 6%,P = 0.003) and a trend toward a higher percentage of reactivity with sarcoma (55% versus 27%,P >0.05). This antibody, therefore, defines a molecule that is a member of the mucin-like epithelial membrane antigen family. Further studies are warranted to determine its usefulness in antibody-directed cancer diagnosis, prognosis, and immunotherapy.     

Detection of lymphocytic choriomeningitis virus antibody in colonies of laboratory animals in Japan

Indirect fluorescent antibody method was applied for a detection of lymphocytic choriomeningitis virus (LCMV) antibody in colonies of laboratory animals in Japan. The results showed that the antibody exist in SPF mice (3/152, 2.2%) and conventional mice (30/539, 5.6%) with the titers ranging from 1:10 to 1:160. The antibody was also detected in 2.2% (2/89) of Syrian hamsters, and 2.9% (2/68) of Apodemus agrarius, 21.4% (3/14) of Japanese harvest mice which have been maintained as laboratory colony for several years. However, the antibody was not demonstrated in Mongolian gerbils, Suncus murinus, guinea pigs and rats, thus far. These results indicate that LCMV infection is present in laboratory animals in Japan, and pointed out the importance of microbiological monitoring for LCMV.     

N- 乙酰转移酶NAT10 在软组织肿瘤中的表达及意义

目的：观察N-乙酰转移酶NAT10蛋白在软组织肉瘤中的表达及与类型、分级的关系。方法：通过原核表达NAT10蛋白免疫制备特异性多克隆抗体,并经免疫印迹鉴定;以组织芯片一免疫组化检测166例软组织肉瘤和28例良性肿瘤及瘤样病变中NAT10蛋白的表达。结果：制备多克隆抗体经Western印迹鉴定与NAT10具有特异结合性。免疫组化显示166例软组织肉瘤中NAT10蛋白阳性95例,阳性率为57％（95／166）,28例良性肿瘤及瘤样病变中4例阳性14％（4／28）。两者间有显著性差异（P〈0．05）。NAT10表达的主要分布为：滑膜肉瘤76％（13／17）、恶性纤维组织细胞瘤75％（15／20）、原始神经外胚叶瘤（PNET）70％（16／23）、横纹肌肉瘤70％（7／10）、恶性外周神经鞘膜瘤50％（11,／22）、隆突性皮肤纤维肉瘤50％（7／14）、平滑肌肉瘤43％（6／14）、脂肪肉瘤42％（8／19）、黏液性纤维肉瘤38％（6／16）。统计比较显示：滑膜肉瘤与黏液性纤维肉瘤和脂肪肉瘤,以及恶性纤维组织细胞瘤与黏液性纤维肉瘤之间NAT10表达具有显著性差异（P〈0．05）;而其它各组间无明显差异（P〉0．05）。同时,NAT10蛋白强阳性表达（≥＋＋）多存在于滑膜肉瘤（53％,9／17）、横纹肌肉瘤（40％,4／10）及恶性纤维组织细胞瘤（40％,8／20）。在FNCLGC分级中,19例I级肉瘤中NAT10阳性表达率为42％（8／19）,44例Ⅱ级肉瘤为43％（19／44）,70例Ⅲ级肉瘤为73％（51／70）。Ⅲ级NAT10阳性率显著高于Ⅱ级组和Ⅰ级组（均为P〈0．05）。结论：研究表明N-乙酰转移酶NAT10表达于多种人软组织肉瘤,尤其在高度恶性肉瘤,因此有可能为软组织肉瘤的分级及预后因子。     

Laminin increases the release of type IV collagenase from malignant cells

We have studied the effect of laminin on type IV collagenolytic activity elaborated by malignant cells in culture. Laminin (at concentrations of 4-8 micrograms/ml) added to serum-free culture supernatants of subconfluent A2058 human melanoma cells significantly increased the release of the type IV collagenolytic activity (200-300%). The induction of type IV collagenase was more pronounced (580%) using a fragment of laminin which binds to the cell surface laminin receptor. A monoclonal antibody against the human laminin receptor blocked the effect of laminin on type IV collagenase, suggesting that occupation of the laminin receptor may be necessary for the effect. Increase in the type IV collagenolytic activity mediated by laminin was also demonstrated in two other malignant cell lines, HT fibrosarcoma (168%) and mouse melanoma (B16-F10) (271%). The increase in type IV collagenase was found to be specific for laminin because another cell-binding matrix protein, fibronectin, did not have any effect, and epidermal growth factor and transferrin actually decreased the type IV collagenase in human melanoma culture medium (epidermal growth factor, 50% at 20 ng/ml; and transferrin, 20% at 10 micrograms/ml). These studies suggest that tumor cell binding to laminin, which comprises the first step of basement membrane invasion, will induce the second step, namely the collagenolytic dissolution of the basement membrane.     

Late development of tumors in the liver of dogs after long-term external gamma-radiation

Development of tumors in the liver of dogs exposed to gamma-quanta for 3 and 6 years at dose--rates of 0.0006, 0.0017 and 0.0034 Gy/day was studied 1-10 years after termination of the exposure. The results are summarized in this work. Tumors were found in 27 out of 89 dogs. The number of benign and malignant tumors was virtually the same (13 and 14). In the first place were hepatoma, among benign neoplasms (9 out of 13), and liver cancer, among malignant tumors (12 out of 14). Neoplasms were more frequent (32%) in exposed animals than in the controls (19%). Tumors were almost two times more frequent and developed earlier after 6 year- than after-3-year-irradiation.     

Ki-67 antibody immunostaining in benign and malignant human prostatic disease.

Indices of mitotic potential may improve prognostic discrimination in patients with malignant disease. Ki-67 is a monoclonal antibody directed against an unknown proliferation antigen which has been shown to be a measure of mitotic potential. Sixty-four benign and eighty malignant prostatic biopsies were stained with the Ki-67 antibody. Nuclear and cytoplasmic staining was identified in benign and malignant biopsies using immunoalkaline phosphatase and immunoperoxidase staining reactions. Nuclear staining was identified in 14 benign and 44 malignant biopsies. Nuclear staining for Ki-67 was seen in 36% of biopsies with Gleason histological score (GHS) 2-4, 71% with GHS 5-7 and 62% with GHS 8-10. Nuclear staining was associated with advanced local disease stage, but not with metastatic disease stage. Clinical follow-up is required to establish the value of Ki-67 immunostaining as a prognostic determinant in prostatic cancer.     

BK antibody and virus-specific IgM responses in renal transplant recipients,patients with malignant disease,and healthy people.

Haemagglutination-inhibition (HAI) antibodies to BK virus, including BK-virus-specific IgM, were determined before and after renal transplantation in 20 patients, in 57 patients with malignant disease, and in 66 healthy controls, Before transplantation 11 of the renal transplant recipients were seronegative, but eight later serocconverted, two before and six after transplantation. Twenty of the patients with malignant disease and 22 controls were also seronegative. The geometric mean titre of BK HAI antibodies was significantly higher among transplanted patients (1/180) than among controls (1/90). BK-virus-specific IgM antibody was detected in seven renal transplant recipients, six patients with malignant disease, and 13 healthy controls. In transplant recipients BK-virus-specific IgM antibody usually persisted throughout the duration of the study, and studies on controls from whom second serum samples were available suggested that they too had persistent BK-virus-specific IgM responses. The geometric mean titre of BK-virus-specific IgM HAI antibody was significantly greater in post-transplantation sera (1/223) than in control sera (1/28). The specificity of the detection of BK-virus-specific IgM HAI antibody was confirmed by direct visualisation of antibody by immune electron microscopy. The persistence of BK-virus-specific IgM suggested that BK virus continued to provide an antigenic stimulus. Nevertheless, there was no obvious association between the serological findings and any clinical features, and prospective studies will be needed to elucidate any such association.     

Seroprevalence of Toxoplasma gondii Infection and Characteristics of Seropositive Patients in General Hospitals in Daejeon, Korea

To figure out the epidemiological status and relevance with other diseases in toxoplasmosis, we checked serum IgG antibody titers of 1,265 patients and medical records of seropositive patients. Seropositive rates were 6.6% by latex agglutination test (LAT) and 6.7% by ELISA. No significant differences were detected between sexes and age groups. The peak seroprevalence was detected in the 40-49-year-old age group. According to clinical department, Toxoplasma-positive rates were high in patients in psychiatry, ophthalmology, health management, emergency medicine, and thoracic surgery. Major coincidental diseases in seropositive cases were malignant neoplasms, diabetes mellitus, arthritis, chronic hepatitis B, chronic renal diseases, schizophrenia, and acute lymphadenitis, in the order of frequency. In particular, some patients with chronic hepatitis B and malignant neoplasms had high antibody titers. These results revealed that the seroprevalence of toxoplasmosis in a general hospital-based study was similar to that in a community-based study, and T. gondii seropositivity may be associated with neoplasms, diabetes, and other chronic infections.     

HLA-DR antigen expression on melanoma metastases and the course of the disease

Summary Melanoma cells freshly isolated from regional lymph node metastases of 59 stage II malignant melanoma patients were analyzed by indirect immunofluorescence staining with monoclonal antibody TAL 1B5, detecting the HLA-DR chain. The expression of HLA-A,B,C antigens, using antibody W6/32, was also investigated in 45 of these cases. There were no substantial differences in the course of the disease with respect to the percentage of positive cells.In 13 malignant melanoma patients two to four simultaneous and/or successive metastases (both locoregional and distant-subcutaneous) were analysed for HLA-DR. With simultaneous metastases (7 cases) the percentage of HLA-DR-positive cells was mostly very similar, and in no case was there more than 25% variation. As to successive metastases (9 cases) the percentage of HLA-DR-positive cells remained practically unchanged or decreased during the course of the disease.     

Lymphoma discrimination by computerized triple matrix analysis of list mode data from three-color flow cytometric immunophenotypes of bone marrow aspirates

BACKGROUND: The goal of this study was to evaluate a self-learning algorithm for the computer classification of information extracted from flow cytometric immunophenotype list mode files from high-grade non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and multiple myeloma (MM). Materials and Methods Bone marrow aspirates (BMA) were obtained from untreated NHL (n = 51), HD (n = 9), or MM (n = 13) patients. Bone marrow aspirates were not infiltrated in NHL and HD patients as confirmed by thorough histologic and cytologic investigation; however, MM patients showed an infiltration rate >50% by malignant myeloma cells. Peripheral blood leukocyte (PBL) samples were taken from age-matched healthy volunteers (n = 44) as easily available control material. A second control group of 15 healthy volunteers, from whom BMA and PBL samples were available, allowed us to differentiate whether the observed classification results on malignant samples were due to the malignant process or simply to the inherent differences between BMA and PBL. Bone marrow aspirates and PBL were analyzed by the same immunophenotyping antibody panel (CD45/14/20, CD4/8/3, kappa/CD19/5, lambda/CD19/5). The acquired list mode data files were analyzed and classified by the self-learning triple matrix classification algorithms CLASSIF1 following a priori separation of the data into a learning set and unknown test set. After completion of the learning phase, known patient samples were reclassified and unknown samples prospectively classified by the algorithm. RESULTS: Highly discriminatory information was extracted for the various lymphoma entities. The most discriminating information was encountered in antibody binding, antibody binding ratios, and relative antibody surface density parameters of leukocytes rather than in percentage frequencies of discrete leukocyte subpopulations. Samples from healthy controls were classified as normal in 97.2% of the cases, whereas those of NHL, HD, and MM patients were on average correctly classified in 80. 8% of the cases. CONCLUSIONS: Although no detectable lymphoma cells were present in BMA of NHL and HD patients, the CLASSIF1 classification of the immunophenotypes of morphologically normal cells provided a surprisingly good disease discrimination equal or better than that obtained by examining pathological lymph nodes according to the respective literature. The results are suggestive for a lymphoma-related and disease-specific antigen expression shift on normal hematopoietic bone marrow cells that can be used to discriminate the underlying disease (specificity of unspecific changes), i.e., in this case NHL from HD. Multiple myeloma patients were discriminated by changes on malignant as well as on normal bone marrow cells.     

Transforming growth factor-alpha expression in benign and malignant human prostatic disease.

Investigation of biological variables in prostatic disease may not only prevent patients with a good prognosis being overtreated, but allow better selection of appropriate therapy, and may identify potential targets for novel therapies. This study investigates the growth factor transforming growth factor-alpha (TGF alpha) expression in benign and malignant prostatic biopsies using both radioimmunoassay and immunohistochemistry, considering its role in malignant epithelial transformation and as a prognostic indicator. Biochemical methods were less satisfactory than the more selective immunohistochemical methods, due to the heterogeneity of prostatic tissue. Seventy-one percent of benign biopsies (range 0-18.62ng/mg DNA) and 69% of malignant biopsies (range 0-11.1ng/mg DNA) had detectable levels of TGF alpha using radioimmunoassay. Immunohistochemical staining for TGF alpha identified expression in 15% of benign (4 out of 27) and 53% malignant biopsies (18 out of 34). Positive staining was also identified in premalignant lesions and within stromal elements, thus implying the factor's role in autocrine/paracrine growth and/or malignant transformation. Immunostaining for TGF alpha may enhance detection of premalignant lesions and small foci of malignant glands which are otherwise difficult to identify using standard histopathological techniques.     

Synthesis and radiolabeling of selective high-affinity ligands designed to target non-Hodgkin's lymphoma and leukemia

Selective high-affinity ligands (SHALs) were synthesized as molecular targeting agents for HLA-DR10, a cell surface receptor upregulated on malignant B-cell lymphocytes in non-Hodgkin's lymphoma and leukemia. SHALs are designed to mimic the affinity and selectivity of Lym-1, an antibody that binds to the beta-subunit of HLA-DR10. To bind selectively to HLA-DR10, SHALs were constructed to bind to two adjacent pockets on the surface of the beta-subunit of HLA-DR10 located within an epitope recognized by the Lym-1 antibody. A series of multivalent SHALs with molecular masses of 1500-3000 Da were synthesized using solid/polymer-supported synthesis on chlorotrityl chloride resin in 50-80% yield. To enable their use as radionuclide carriers in mouse studies, SHALs were conjugated to DOTA in a solution-phase reaction with 70-100% yield. 57Co/CoCl2 titrations revealed that 50-60% of the DOTA in the DOTA-conjugated SHALs was available for radiometal chelation. These DOTA-SHALs were labeled with 111In and used to carry out pharmacokinetic studies in mice. Radiolabeling reactions of DOTA-SHALs, with exactly one DOTA entity per targeting SHAL molecule, yielded products with greater than 90% radiochemical purity and specific activities ranging from 97 to 150 muCi/mug.     

Olanzapine-associated neuroleptic malignant syndrome: Is there an overlap with the serotonin syndrome?

BACKGROUND: The neuroleptic malignant syndrome is a rare but serious condition mainly associated with antipsychotic medication. There are controversies as to whether "classical" forms of neuroleptic malignant syndrome can occur in patients given atypical antipsychotics. The serotonin syndrome is caused by drug-induced excess of intrasynaptic 5-hydroxytryptamine. The possible relationship between neuroleptic malignant syndrome and serotonin syndrome is at present in the focus of scientific interest. METHODS: This retrospective phenomenological study aims to examine the seventeen reported olanzapine - induced neuroleptic malignant syndrome cases under the light of possible overlap between neuroleptic malignant syndrome and serotonin syndrome clinical features. RESULTS: The serotonin syndrome clinical features most often reported in cases initially diagnosed as neuroleptic malignant syndrome are: fever (82%), mental status changes (82%) and diaphoresis (47%). Three out of the ten classical serotonin syndrome clinical features were concurrently observed in eleven (65%) patients and four clinical features were observed in seven (41%) patients. CONCLUSION: The results of this study show that the clinical symptoms of olanzapine-induced neuroleptic malignant syndrome and serotonin syndrome are overlapping suggesting similarities in underlying pathophysiological mechanisms.