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Phishing is an attack characterized by attempted fraud against users. The attacker develops a malicious page that is a trusted environment, inducing its victims to submit sensitive data. There are several platforms, such as PhishTank and OpenPhish, that maintain databases on malicious pages to support anti-phishing solutions, such as, for example, block lists and machine learning. A problem with this scenario is that many of these databases are disorganized, inconsistent, and have some limitations regarding integrity and balance. In addition, because phishing is so volatile, considerable effort is put into preserving temporal information from each malicious page. To contribute, this article built a phishing database with consistent and balanced data, temporal information, and a significant number of occurrences, totaling 942,471 records over the 5 years between 2016 and 2021. Of these records, 135,542 preserve the page's source code, 258,416 have the attack target brand detected, 70,597 have the hosting service identified, and 15,008 have the shortener service discovered. Additionally, 123,285 records store WHOIS information of the domain registered in 2021. The data is available on the website https://piracema.io/repository., (© 2022. The Author(s).)

The hand is an important part of the body used to express information through gestures, and its movements can be used in dynamic gesture recognition systems based on computer vision with practical applications, such as medical, games and sign language. Although depth sensors have led to great progress in gesture recognition, hand gesture recognition still is an open problem because of its complexity, which is due to the large number of small articulations in a hand. This paper proposes a novel approach for hand gesture recognition with depth maps generated by the Microsoft Kinect Sensor (Microsoft, Redmond, WA, USA) using a variation of the CIPBR (convex invariant position based on RANSAC) algorithm and a hybrid classifier composed of dynamic time warping (DTW) and Hidden Markov models (HMM), called the hybrid approach for gesture recognition with depth maps (HAGR-D). The experiments show that the proposed model overcomes other algorithms presented in the literature in hand gesture recognition tasks, achieving a classification rate of 97.49% in the MSRGesture3D dataset and 98.43% in the RPPDI dynamic gesture dataset.

Autoassociative artificial neural networks have been used in many different computer vision applications. However, it is difficult to define the most suitable neural network architecture because this definition is based on previous knowledge and depends on the problem domain. To address this problem, we propose a constructive autoassociative neural network called CANet (Constructive Autoassociative Neural Network). CANet integrates the concepts of receptive fields and autoassociative memory in a dynamic architecture that changes the configuration of the receptive fields by adding new neurons in the hidden layer, while a pruning algorithm removes neurons from the output layer. Neurons in the CANet output layer present lateral inhibitory connections that improve the recognition rate. Experiments in face recognition and facial expression recognition show that the CANet outperforms other methods presented in the literature.

The human visual system is one of the most fascinating and complex mechanisms of the central nervous system that enables our capacity to see. It is through the visual system that we are able to accomplish from the most simple task such as object recognition to the most complex visual interpretation, understanding and perception. Inspired by this sophisticated system, two models based on the properties of the human visual system are proposed. These models are designed based on the concepts of receptive and inhibitory fields. The first model is a pyramidal neural network with lateral inhibition, called lateral inhibition pyramidal neural network. The second proposed model is a supervised image segmentation system, called segmentation and classification based on receptive fields. This work shows that the combination of these two models is beneficial, and the results obtained are better than that of other state-of-the-art methods.

Background: Glycophorin C (GPC) is necessary in the maintenance of red blood cell structure. Severe autoimmune hemolytic anemia and hemolytic disease of the fetus and newborn (HDFN) have been associated with Gerbich (Ge) blood group system antigens expressed on GPC. Previous in vitro studies with cord blood progenitor cells have shown that anti-Ge suppresses erythropoiesis., Study Design and Methods: Here, we evaluated the K562 erythroleukemic cell line to study the cellular effects of a murine anti-GPC. Cell proliferation was evaluated after treatment with anti-GPC. Flow cytometry was used to evaluate exofacial phosphatidylserine (PS) expression and cell viability (propidium iodide binding). Cell morphology was evaluated under light microscopy with cytospin preparations stained with May-Grünwald Giemsa., Results: Anti-GPC dramatically inhibited K562 proliferation and increased PS expression, consistent with cytoplasmic blebbing, suggesting evidence of apoptosis. Z-VAD-FMK, an inhibitor of classical apoptosis, was unable to reverse the suppressive effect of anti-GPC. However, hemin was able to attenuate growth suppression., Conclusion: Together, the data suggest that anti-GPC suppresses erythroid proliferation through the induction of nonclassical apoptosis., (© 2012 American Association of Blood Banks.)

Purpose: Adjuvant chemotherapy with cyclophosphamide (CYC) is used for the treatment of breast cancer. CYC is used as a racemic mixture, although preclinical data have demonstrated differences in the efficacy and toxicity of its enantiomers, with (S)-(-)-CYC exhibiting a higher therapeutic index. The present study investigated the enantioselectivity and influence of CYP2B6, CYP2C9, CYP2C19, and CYP3A on the kinetic disposition of CYC in patients with breast cancer., Methods: Fifteen patients previously submitted to removal of the tumor and treated with racemic CYC (900 or 1,000 mg/m(2)) and epirubicin were included in the study. The in vivo activity of CYP3A was evaluated using midazolam as a marker drug. Serial blood samples were collected up to 24 h after administration of the first cycle of CYC., Results: The kinetic disposition of CYC was enantioselective in patients with breast cancer, with plasma accumulation of the (S)-(-)-CYC enantiomer (AUC 195.0 vs. 174.8 μg h/mL) due to the preferential clearance of the (R)-(+)CYC enantiomer (5.1 vs. 5.7 L/h). Clearance of either CYC enantiomer did not differ between the CYP2B6, CYP2C9, and CYP2C19 genotypes or as a function of the in vivo activity of CYP3A evaluated by midazolam clearance., Conclusions: The pharmacokinetics of CYC is enantioselective in patients with breast cancer concomitantly treated with epirubicin and ondansetron. Genotyping or phenotyping did not contribute to adjustment of the CYC dose regimen in patients included in this study.

Aim: This study investigated the kinetic disposition, metabolism and enantioselectivity of albendazole (ABZ) and praziquantel (PZQ) administered alone and in combination to healthy volunteers., Methods: A randomized crossover study was carried out in three phases (n= 9), in which some volunteers started in phase 1 (400 mg ABZ), others in phase 2 (1500 mg PZQ), and the remaining volunteers in phase 3 (400 mg ABZ + 1500 mg PZQ). Serial blood samples were collected from 0-48 h after drug administration. Pharmacokinetic parameters were calculated using a monocompartmental model with lag time and were analyzed using the Wilcoxon test; P ≤ 0.05., Results: The administration of PZQ increased the plasma concentrations of (+)-ASOX (albendazole sulphoxide) by 264% (AUC 0.99 vs. 2.59 µg ml(-1) h), (-)-ASOX by 358% (0.14 vs. 0.50 µg ml(-1) h) and albendazole sulfone (ASON) by 187% (0.17 vs. 0.32 µg ml(-1) h). The administration of ABZ did not change the kinetic disposition of (+)-(S)-PZQ (-)-(R)-4-OHPZQ or (+)-(S)-4-OHPZQ, but increased the plasma concentration of (-)-(R)-PZQ by 64.77% (AUC 0.52 vs. 0.86 µg ml(-1) h)., Conclusions: The pharmacokinetic interaction between ABZ and PZQ in healthy volunteers was demonstrated by the observation of increased plasma concentrations of ASON, both ASOX enantiomers and (-)-(R)-PZQ. Clinically, the combination of ABZ and PZQ may improve the therapeutic efficacy as a consequence of higher concentration of both active drugs. On the other hand, the magnitude of this elevation may represent an increased risk of side effects, requiring, certainly, reduction of the dosage. However, further studies are necessary to evaluate the efficacy and safety of this combination., (© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.)

The pharmacokinetics of cyclophosphamide (CYC) enantiomers were evaluated in patients with lupus nephritis distributed in 2 groups according to creatinine clearance: group 1 (90.6-144.6 mL/min/1.73 m(2)) and group 2 (42.8-76.4 mL/min/1.73 m(2)). All patients were treated with 0.75 to 1.3 g of racemic CYC as a 2-hour infusion and with 1 mg intravenous midazolam as a drug-metabolizing marker. CYC enantiomers and midazolam concentrations in plasma were measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS). The following differences (Wilcoxon test, P < or = .05) were observed between the (S)-(-) and (R)-(+) enantiomers: AUC(0-infinity) 152.41 vs 129.25 microg.h/mL, CL 3.28 vs 3.89 L/h, Vd 31.38 vs 29.74 L, and t((1/2)) 6.79 vs 5.56 h for group 1 and AUC(0-infinity) 167.20 vs 139.08 microg.h/mL, CL 2.99 vs 3.59 L/h, and t((1/2)) 6.15 vs 4.99 h for group 2. No differences (Mann test, P < or = .05) were observed between groups 1 and 2 in the pharmacokinetic parameters of both enantiomers. No significant relationship was observed between midazolam clearance (2.92-16.40 mL/min.kg) and clearance of each CYC enantiomer. In conclusion, CYC kinetic disposition is enantioselective, resulting in higher exposures of the (S)-(-) enantiomer in lupus nephritis patients, and the pharmacokinetic parameters of both enantiomers are not altered by the worsening of renal condition.

This article describes the enantioselective analysis of cyclophosphamide (CPA) in human plasma using LC-MS/MS. CPA enantiomers were extracted from plasma using a mixture of ethyl acetate and chloroform (75:25, v/v). The enantiomers were separated on a Chiralcel(R) OD-R column, with the mobile phase consisting of a mixture of acetonitrile and water (75:25, v/v) plus 0.2% formic acid. The protonated ions and their respective product ions were monitored using two functions, 261 > 141 for CPA enantiomers and 189 > 104 for the internal standard (antipyrine). Recovery rates were higher than 95% and the quantification limit was 2.5-ng/ml plasma for both enantiomers. The coefficients of variation and the relative errors obtained for the validation of intra- and interassay precision and accuracy were less than 10%. The method was applied for the investigation of the enantioselective pharmacokinetics of CPA in a lupus nephritis patient treated with 1 g CPA infused over 2 h and in a breast cancer patient treated with 0.9 g infused over 1 h. No stereoselectivity in the pharmacokinetic parameters was observed for either patient. Clearance values of 2.63 and 2.93 l/h and of 3.36 and 3.61 l/h for (-)-(S) and (+)-(R)-CPA were obtained for the breast cancer and lupus nephritis patient, respectively., ((c) 2008 Wiley-Liss, Inc.)

Objective: To identify the types of requests, the patterns of testing, and the error rates associated with the genetic identification of fetuses at risk for immune-mediated hemolytic disease., Method: Retrospective review of the laboratory information system for all fetal blood group genotyping tests performed at Mount Sinai Hospital, Toronto, Canada from January 1997 to December 2006., Results: Amniotic fluid-derived DNA, from 220 women (243 pregnancies), was tested for one or more antigens (279 tests) when the father was heterozygous for the inferred blood group antigen or was unavailable. The PCR amplification failure rate of amniotic fluid-derived DNA was 5.0%. When the father was considered hemizygous for RHD or was not available, the fetus was positive in 68.6% and 72.7% of cases, respectively. Two amniotic fluid-derived DNA KEL1 SSP-PCR results did not correlate with the result determined from cultured amniocyte DNA., Conclusions: Paternal RHD hemizygosity may be overestimated. Thus, we recommend that RHD zygosity be established by molecular analysis of the RHD breakpoint. Cultured amniocytes should be reserved for testing if the amniotic fluid-derived DNA is inconclusive due to PCR amplification failure. We use PCR-RFLP genotyping methods for RHCE*E/RHCE*e (Rh E/e), KEL1/KEL2 (K/k), FYA/FYB (Fy(a/b)), and JKA/JKB (Jk(a/b)).

Blood group genotyping using DNA extracted from fetal tissue is useful to identify fetuses at risk for hemolytic disease of the fetus and newborn (HDFN) due to maternal red cell alloantibodies. Four considerations are important for fetal blood group genotyping. First, paternal heterozygosity must be established, including tests that evaluate RHD hemizygosity. Second, the source of fetal tissue for DNA extraction requires certain considerations. Third, because the fetal genotype is used to predict the expressed phenotype, a thorough knowledge of blood group genetics is required. Moreover, the test algorithm should include the evaluation of the parental phenotypes and genotypes to help identify variant alleles. Fourth, the blood group antigen expression at birth should be evaluated to confirm the inheritance. The identification of an antigen-negative fetus on the basis of the blood group genotype provides significant advantages in managing the pregnancy at risk for HDFN. In the near future, fetal DNA in maternal plasma will likely replace fetal blood group genotyping for RHD. Significant challenges remain to detect other clinically significant blood group antigens using maternal plasma DNA.

Objectives: Assessing the number of fetal cells in the maternal circulation quantifies the volume of feto-maternal hemorrhage, enhancing the ability to provide effective prevention of Rhesus (Rh) allommunization and appropriate fetal surveillance in cases of significant feto-maternal hemorrhage., Methods: Having developed a standard curve with maternal samples spiked with known volumes of fetal red blood cells, we used a flow cytometric method using fluorescent labeled antihemoglobin F to quantitate fetal cells in the maternal circulatory system in two groups of women undergoing chorionic villus sampling (CVS), by either biopsy forceps or cannula aspiration (n = 170 women). We compared these results with the gold standard, the Betke-Kleihauer test., Results: Our results show good correlation between the flow cytometric method and the traditional Betke-Kleihauer method for fetal red cell quantitation (r(2) = 0.99). Fetal red blood cells were identified in 10 women by the Betke-Kleihauer method, and in 26 women by flow cytometry. CVS was not associated with an increase in feto-maternal hemorrhage., Conclusion: Flow cytometry was both more sensitive and more timely for the quantitation of feto-maternal hemorrhage than was Betke-Kleihauer.

The analysis of albendazole sulfoxide, albendazole sulfone, praziquantel and trans-4-hydroxypraziquantel in plasma was carried out by high-performance liquid chromatography-mass spectrometry ((LC-MS-MS). The plasma samples were prepared by liquid-liquid extraction using dichloromethane as extracting solvent. The partial HPLC resolution of drug and metabolites was obtained using a cyanopropyl column and a mobile phase consisting of methanol:water (3:7, v/v) plus 0.5% of acetic acid, at a flow rate of 1.0 mL/min. Multi reaction monitoring detection was performed by electrospray ionization in the positive ion mode, conferring additional selectivity to the method. Method validation showed relative standard deviation (precision) and relative errors (accuracy) lower than 15% for all analytes evaluated. The quantification limit was 5 ng/mL and the linear range was 5-2500 ng/mL for all analytes. The method was used for the determination of drug and metabolites in swine plasma samples and proved to be suitable for pharmacokinetic studies.

Background: The D antigen includes category D, partial D, and weak D types, which are important because anti-D alloimmunization can occur in some but not all persons that express a variant RHD allele. At present, there is little prospective information on the prevalence of D variants among obstetric patients and potential transfusion recipients., Study Design and Methods: The RHD alleles were prospectively examined in a large patient population identified on the basis of a difference in anti-D reactivity between two reagents., Results: Fifty-five discrepancies (0.96% of D-) were noted among 33,864 ethnically diverse patients over 18 months, of which 54 represented mutated RHD alleles. Seven obstetric patients were assigned D- status based on serology; only 1 patient had a partial RHD allele. Ten of 25 (36%) obstetric patients and 4 of 6 (67%) female potential transfusion recipients of childbearing age or younger were assigned D+ status, and they expressed a D variant known to permit anti-D alloimmunization. In total 20 RHD alleles were identified including category, DVa or DVa-like alleles (n = 7), DAR (n = 8), and four novel RHD alleles including two new DAU alleles., Conclusion: Given the complexity of D antigen expression, it is concluded that some clinically important D variants identified by standard serologic analysis phenotype as D+ and are potentially at risk for the development of anti-D.

Objective: This trial compared two instruments for transcervical chorionic villus sampling (CVS)., Design: Randomised controlled trial., Setting: Regional university prenatal diagnosis and treatment centre., Population: Two hundred women were randomised at 10(+0)-12(+6) weeks of gestation to transcervical CVS using cannula aspiration (CA) or biopsy forceps (BF)., Methods: Women undergoing indicated CVS signed informed consent. Randomisation after decision to perform transcervical CVS., Primary Outcome: the rise in maternal serum alpha-fetoprotein (alpha-FP)., Secondary Outcomes: (i) placental trauma (fetomaternal haemorrhage [FMH]); (ii) laboratory, procedure, and cytogenetic results and pregnancy outcomes; (iii) patient and operator satisfaction; and (iv) economic analyses. Analyses were performed by intention to treat., Results: The -FP rise did not differ between groups; there was no other evidence of placental trauma. BF were better tolerated by women, provided culturable tissue, after fewer instrument passes, with greater ease and in less time. BF were associated with cost savings., Conclusions: Unlike -FP, other markers of FMH were unaltered, questioning the reliability of alpha-FP as an indicator of FMH. Compared with CA, transcervical BF caused comparable placental trauma, appeared to be similarly effective and safe and were preferred by operators and patients.

Background: Clinically significant antibodies to high-incident antigens present a challenge in hemolytic disease of the newborn. Antigen-negative blood may be difficult to obtain for intrauterine transfusion (IUT). In these instances, maternal blood is de facto compatible regardless of an ABO mismatch., Case Report: A group B/D-- woman with a history of hemolytic disease of the newborn due to anti-Rh17 (titer 256) presented to the obstetrical clinic at 12 weeks gestation for management of her third pregnancy. She consented to donate blood for possible IUT., Study Design and Methods: Washed maternal packed cells were suspended in saline to 75 percent Hct and irradiated before transfusion. The fetus was transfused via the intrahepatic vein., Results: Ultrasound examination at 19 weeks indicated a hydropic fetus. The fetal blood group was O Rh+, direct antiglobulin test 4+, and hemoglobin 22 g per L. A total of 368 mL of maternal blood was transfused during seven procedures. Labor was induced at 38 weeks, and a 2560-g male infant was delivered by Caesarian-section due to fetal distress. The infant grouped as B Rh+, direct antiglobulin test negative. No group O red blood cells were detected. The hemoglobin level was 143 g per L rising to 209 g per L at discharge 3 days later. The indirect bilirubin was 55 micromol/L and remained stable during the hospital stay. Phototherapy was discontinued after 1 day, and the infant was discharged without an exchange or top-up transfusion., Conclusions: Maternal ABO-mismatched blood is an alternate source for IUT in instances when antigen-compatible allogenic blood is unavailable.

The neonatal Fc receptor (FcRn) is a key receptor involved in the transcytosis of IgG across the maternal-fetal barrier. The level of IgG varies considerably among newborn infants. Since other Fc gamma receptors show single nucleotide functional variants, we determined whether common variant alleles exist for the FcRn. Direct sequence analysis was performed on PCR-amplified complementary DNA (cDNA) isolated from ten placental mRNAs (20 alleles examined). Two synonymous nucleotide polymorphisms were detected from the same source. A G251T and C707T substitution, reflecting amino acid positions Pro19 and Arg171 of the mature polypeptide, did not alter the amino acid encoded. No other nucleotide substitutions or sequence variations were observed. Thus, the variation in IgG transport is not due to common variant alleles among the human population. Due to the limited number of samples tested (n=20), low-frequency alleles would go undetected by chance alone when q has a frequency < or = 0.14. It is unlikely that low-frequency variant alleles, if present, are responsible for the major variation seen in the transcytosis of IgG.

Objective: The purpose of this study was to histologically characterize a series of oral non-Hodgkin's lymphomas (NHLs) and to investigate latent and lytic Epstein-Barr virus (EBV) infection in these., Study Design: The revised European-American Lymphoma classification system (41) was used to categorize 58 cases of oral NHL, which included 9 immunosuppression-related NHLs. EBV infection was determined by in situ hybridization for Epstein-Barr virus-encoded RNA and by immunohistochemistry for the EBV antigens latency membrane protein, Epstein-Barr nuclear antigen-2 (EBNA2) and Z EBV replication activator protein., Results: Most tumors were B-cell lymphomas (78%), but the proportion of T-cell lymphomas was surprisingly high (22%). The most common histologic subtypes were diffuse large B-cell lymphomas (45%), peripheral T-cell lymphomas (19%), and follicle center lymphomas (14%). Two thirds of the known immunosuppression-related NHLs were T-cell lymphomas. All of the immunosuppression-related tumors were EBV-infected, whereas the EBV infection rate in the NHLs of the remaining patients presumed to be immunocompetent was only 9%. Most EBV-positive tumors expressed neither of the latent antigens (ie, latency membrane protein and Epstein-Barr nuclear antigen-2), and coexpression of the 2 was observed only in immunosuppressed patients. Z EBV replication activator protein expression, which is indicative of replicative infection, occurred only in immunosuppressed individuals., Conclusions: Diffuse large B-cell lymphomas were the most common histologic subtype of oral NHLs, but T-cell lymphomas were relatively common and frequently occurred in states of immunosuppression. EBV may play a limited role in the initiation of lymphoma in the immunocompetent patient, but the virus may be of importance in progression of the disease in those patients with more aggressive tumors, as immunosuppression occurs.

This study is the first test of the novel hypothesis that perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) marks an etiological division between stress-susceptible and stress-neutral ulcerative colitis. Subjects were 47 UC patients with known p-ANCA status (19 p-ANCA-positive, 28 p-ANCA-absent). Controls were 77 university students. Subjects and controls completed the Reciprocal Attachment Questionnaire. Subjects were categorized as avoidant/nonavoidant and anxious/nonanxious based on scores for compulsive self-reliance and compulsive care seeking, respectively. A higher prevalence of avoidant attachment was present in p-ANCA-absent (58.6%) than p-ANCA-positive subjects (22.2%, chi-square = 5.95, P < 0.02). There was no difference in the prevalence of anxious attachment between p-ANCA-absent and p-ANCA-positive subjects. There was no difference in clinical and psychiatric variables between groups. This finding provides support for a psychobiological contribution to UC in a subgroup identified by the absence of p-ANCA.

How three hematology laboratories improved efficiency by automating the preanalytical process, reorganizing lab workspace, using data management systems to identify which samples need further verification, and setting strict criteria limiting the need for nonautomated processes.

An 80-year-old woman presented with fevers, night sweats, and weight loss. Her serum CA-125 level was markedly elevated (380 U/mL; normal < 35 U/ml). At post-mortem examination, the patient had widespread intermediate-grade malignant lymphoma with extensive infiltration of the greater omentum and pelvic peritoneum. Immunohistochemistry for CA-125 documented intense staining in the reactive mesothelial cells of the peritoneum; the tumor cells were not immunoreactive. CA-125 is a glycoprotein recognized by a monoclonal antibody raised against an ovarian-cancer cell line. Elevated levels have been reported rarely in patients with malignant lymphoma, and the pathophysiology of this finding has not been understood. Our data support the hypothesis that elevated CA-125 levels may reflect production by reactive mesothelium in patients with benign or malignant diseases involving the peritoneum, including malignant lymphoma. The clinical application of this marker, therefore, is broader than the recognized monitoring of patients with ovarian carcinoma.

The effects of sublethal radiation (3 Gy) and anti-asialo GM1 (anti-ASGM1) on engraftment of human tumour cell lines and fresh tumour were evaluated in the severe combined immunodeficient (SCID) mouse. Four tumour cell lines (colonic adenocarcinoma LS174T, malignant melanoma MEWO, lung adenocarcinoma H125, chronic myelogenous leukemia K562) and a fresh colon cancer metastasis were injected subcutaneously, intraperitoneally or intravenously into SCID mice. Tumour volume and metastatic spread of implanted tumours were evaluated 3-8 weeks following inoculation. Pretreatment with radiation and anti-ASGM1 resulted in more rapid and extensive uptake of subcutaneous and intraperitoneal tumours. Tail vein injection into pretreated animals also resulted in a greater number of lung metastases of H125, MEWO and K562 cell lines. This study demonstrates that sublethal radiation and the elimination of murine NK cell activity with anti-ASGM1 improves tumour take rates. These findings should prove useful for investigations of human cancer immunotherapy using SCID mice engrafted with human lymphocytes and human tumours.

The severe combined immunodeficient (SCID) mouse engrafted with human peripheral blood lymphocytes (PBLs) is a potentially useful model for the study of cancer immunotherapy. For this application, rapid, consistent, and high level engraftment of SCID mice with functional human cytotoxic effector cells is necessary. To date, short term human lymphoid cell engraftment in SCID mice has generally been low and variable. Further, most of the human cells detected within the first 30 days are found in the peritoneal cavity. The purpose of the present study was to improve short term reconstitution of human PBLs in the SCID mouse. When untreated SCID mice were injected with human PBLs, the mean level of CD3+ cells in the spleens was < 5% on days 6-32 after injection, as determined by flow cytometry (FCM). Depletion of SCID mouse natural killer (NK) cells with anti-asialo GM1 only marginally improved short term reconstitution with human CD3+ cells. Preirradiation of SCID mice with 3 Gy improved reconstitution to over 16% CD3+ cells on days 12-14 following engraftment. However, the combination of pretreatment with anti-asialo GM1 plus radiation, significantly increased the mean percentage of human CD3+ cells in the spleen to 40% within 2 weeks following injection of PBLs. Human T cells positive for CD4, CD8, TcR alpha beta, and TcR gamma delta, and human NK and B cells were detected in the spleens of irradiated plus anti-asialo GM1 pretreated SCID mice. The presence of human lymphoid cells was confirmed by immunohistologic staining. The human immune cells in these mice were shown to be functional by the in vivo demonstration of an appropriate secondary immune response to the injection of tetanus toxoid and by an in vivo proliferative response to phytohemagglutinin. Human NK cells could be found in the spleens and peripheral blood of irradiated plus anti-asialo GM1 pretreated mice. These cells were also shown to be competent by their ability to lyse the human NK sensitive tumor targets K562 and MOLT-4 in 51Cr release assays. Thus, pretreatment of SCID mice with radiation plus anti-asialo GM1 significantly improves short term human PBL engraftment and provides a potentially useful model for the study of cancer immunotherapy.

Objective: To evaluate the diagnosis and management of patients with malignant lymphoma of bone., Design: A case series review in which the minimum follow-up was 24 months and the mean follow-up was 49 months., Setting: All patients were managed at a tertiary care centre, although initial biopsies were often done in community centres., Patients: Selected for review were 15 of 18 consecutive patients who were referred to the Musculoskeletal Oncology Unit at the Mount Sinai Hospital, Toronto, between 1984 and 1989, with a bone lesion as the presenting symptom of lymphoma. The three excluded patients included two with diffuse nodal disease at presentation and one who had a second, unrelated malignant tumour., Interventions: Staging studies (hematologic investigations, radiography, technetium bone scanning and computed tomography), surgical biopsies of the lesion, chemotherapy, radiotherapy and in some cases surgical resection of the lesion., Main Outcome Measures: The number of biopsies required for diagnosis and the incidence of complications that required operative intervention., Results: Seven of the 15 patients required more than one biopsy to establish the diagnosis. Five patients required surgical procedures for late complications that included pathologic fractures, wound infection and osteonecrosis. At 24 months' follow-up, 13 patients were disease free and 2 had died., Conclusions: Proper biopsy and pathological evaluation are crucial in the diagnosis of lymphoma of bone. These measures will decrease the necessity for repeat biopsies. Lymphoma is best managed medically. Surgery should be reserved for biopsy and for treatment of the complications of therapy.

We describe a case of inflammatory and degenerative arthritis treated with intraarticular corticosteroid injections. This led to rapid subjective relief of symptoms, but inappropriate repeated injections led to the development of Charcot's arthropathy and rapid destruction of the shoulder joint.

DNA content and estrogen-receptor status were studied in 54 consecutive patients with primary breast carcinoma. Estrogen-receptor determinations were performed by immunohistochemical assay on frozen sections with a monoclonal antibody against the estrogen-receptor molecule and by biochemical analysis with a dextran-coated charcoal method. Nuclear DNA content was measured by flow cytometry performed on formalin-fixed, paraffin-embedded sections. Seventy-two percent of tumours were positive for estrogen receptors by immunohistochemical assay and 67% by biochemical assay. Comparison of the qualitative results of immunohistochemical and biochemical estrogen-receptor determinations revealed a strong correlation between the two assays, with agreement in 90% of the cases (p less than 0.001). Regression analysis showed only a weak relationship between the quantitative results of the two assays. DNA analysis was performed in 51 cases, and 54% demonstrated aneuploid stemlines by flow cytometry. An association was demonstrated between aneuploidy and low levels of estrogen receptor. The association was highly significant with the immunohistochemical assay but not with the biochemical assay. The authors' results suggest that immunohistologic determinations of estrogen receptor status may better reflect the biologic features of the tumour cells. However, improved standardization in reporting the results is necessary if the test is to have widespread use.

Flow cytometry was applied to the analysis of DNA contents in 59 cases of breast cancer, among which 28 cases were diploidy cancers, and 31 were aneuploid. DNA index of these cases was found to be ranging from 0.45 to 3.35, including S-phase fraction (SPF) from 2.46% to 78.87%, and proliferation index (PI) from 17.06 to 87.04. In 60 cases of breast carcinoma, nuclear estrogen receptors (ERn) were assayed by immunocytochemistry with ER-monoclonal antibody. 29 of them were ERn-, and 31 were ERn+. The DNA contents and ERn levels, both detected in each of 57 cases, were found to be correlated to some extent. In aneuploidy cancer group, there were more ERn- cases than ERn+ cases (P less than 0.05). The mean value of PI was higher in the ERn- group than in the ERn+ group, and the corresponding ERn- cases were more frequent with increase of PI value. Among those cases in which SPF was over 40%, there were more ERn- cases than ERn+ cases. The relations between ERn levels and DNA contents may represent the degree of differentiation of breast cancers and may help to predict prognosis.

Among 63 patients with intermediate or high grade non Hodgkin's lymphoma (NHL) seen at our institution in a five-year period, 19 were aged 70 years or older. For various reasons, four of these patients were either not treated or received only minimal treatment. Three of the patients remain well without evidence of disease for 1 to 3 years, and the fourth has relapsed in an indolent fashion after 3 years. These observations suggest that existence of a subset of patients with histologically aggressive non-Hodgkin's lymphoma whose disease behaves mildly. Because of the high incidence of treatment-related morbidity and mortality in elderly lymphoma patients treated with combination chemotherapy, it is important to try to identify prospectively this subset of patients clinically and to avoid overtreatment in this category of cases.

Nonchromaffin paraganglioma (NCP), also called glomus body tumor or chemodectoma, is rarely found in the orbit. The behavior of orbital nonchromaffin paraganglioma may potentially be more aggressive than in other head and neck locations. Diagnosis depends on electron microscopic demonstration of membrane-bound neurosecretory granules. Results of histopathologic study show a well-circumscribed lesion without a true capsule with alveolar or organoid arrangements of epithelioid cells within a reticulin framework with thin-walled blood vessels. Cells are polygonal with round or oval nuclei containing rare mitotic figures and pale-staining cytoplasm. Differential diagnosis includes alveolar soft-part sarcoma, alveolar rhabdomyosarcoma, neuroblastoma, carcinoid, and granular cell tumor. Of 29 previously reported cases of orbital NCP, 16 have been reclassified as alveolar soft-part sarcoma. The authors report a patient with an electron microscopically established orbital NCP, with the history of a contralateral glomus jugulare tumor irradiated 14 years previously.

Alaria americana is a trematode, the adult of which is found in mammalian carnivores. The first case of disseminated human infection by the mesocercarial stage of this worm occurred in a 24-year-old man. The infection possibly was acquired by the eating of inadequately cooked frogs, which are intermediate hosts of the worm. The diagnosis was made during life by lung biopsy and confirmed at autopsy. The mesocercariae were present in the stomach wall, lymph nodes, liver, myocardium, pancreas and surrounding adipose tissue, spleen, kidney, lungs, brain and spinal cord. There was no host reaction to the parasites. Granulomas were present in the stomach wall, lymph nodes and liver, but the worms were not identified in them. Hypersensitivity vasculitis and a bleeding diathesis due to disseminated intravascular coagulation and a circulating anticoagulant caused his death 8 days after the onset of his illness.

A case of diffuse lymphomatous polyposis of the gastrointestinal tract is reported. The patient presented with abdominal pain and weight loss and x-rays revealed multiple polyps involving the entire gastrointestinal tract. Biopsies confirmed the diagnosis of lymphomatous polyposis. The patient also had involvement of the bone marrow and supraclavicular lymph node. Immunologically this lymphoma was characterized as a monoclonal proliferation of B lymphocytes bearing immunoglobulin M, type kappa. Diffuse lymphomatous polyposis of the gastrointestinal tract appears to be a generalized malignancy of uncommitted B cells of Peyer's patches. The migratory properties of these cells may account for the tendency to dissemination of lymphomatous polyposis. Diffuse lymphomatous polyposis of the gastrointestinal tract is a distinct entity, separate from the diffuse gastrointestinal lymphoma known as Mediterranean-type lymphoma.

A case of retrovirus-associated adult T-cell lymphoma studied by monoclonal markers and ultrastructure is reported. The patient, who was born in Jamaica and emigrated to Canada 9 years previously, had a 5-year history of asymptomatic lymphocytosis preceding the onset of rapidly progressive disease. The peripheral blood lymphocytes were predominantly pleomorphic small lymphocytes with a smaller population of transformed lymphocytes. The peripheral blood lymphocytes were typed immunologically as T-cells of helper/inducer phenotype. Immunological typing of the lymph node lymphocytes, performed on tissue sections, demonstrated a similar phenotype. Morphological study of the lymph node showed a diffuse lymphoma, encompassing a wide range of cell sizes, including giant cells. In view of the morphological heterogeneity of this condition, immunological and viral studies are recommended to confirm the diagnosis.

The autopsy of an infant with the 4p- or Wolf-Hirschhorn syndrome revealed visceral abnormalities not previously described, i.e., agencies of the gallbladder and spleen. The parents' chromosomes were normal.

A 67-year-old woman presented with supraclavicular lymphadenopathy, a large mediastinal mass, marrow plasmacytosis, and paraproteins, including free lambda light chains, in the serum and urine. Biopsies of the lesions demonstrated nodular amyloidosis, which was confirmed by ultrastructural and cytochemical analyses. Immunoperoxidase staining indicated that the amyloid was composed of lambda light chains. Nodular mediastinal amyloidosis is a rare manifestation of amyloidosis and appears to be a form of immunocytic amyloidosis.

A black, West Indian woman with adult T-cell leukemia-lymphoma (ATLL), hypercalcemia, peripheral and retroperitoneal lymphadenopathy, and serum antibodies to human T-lymphotropic virus (HTLV) was found to have massive mediastinal adenopathy, a feature not previously reported in patients with ATLL. In addition, she had had asymptomatic leukocytosis with marked lymphocytosis for at least 6 years before presenting with full-blown ATLL. These findings broaden the clinical picture of ATLL. Cell surface-marker studies and close follow-up are recommended for patients with apparent chronic lymphocytic leukemia, especially if they have pleomorphic lymphocytosis, are younger than usual or are from the Caribbean or Japan.

Renal disease is a common complication of paraproteinemia, but light-chain nephropathy with resultant Fanconi's syndrome is unusual. In a 60-year-old man with Fanconi's syndrome, the underlying disease was a well-differentiated lymphocytic lymphoma, with two paraproteins and lambda-light-chain proteinuria. A renal biopsy specimen showed crystals in tubular cells, more prominent in proximal than distal tubules. Immunoperoxidase studies confirmed the lambda-light-chain content of the crystals. All previous cases studied by biopsy have involved kappa light chains. Light chains are thought to be toxic to the tubular epithelium, resulting in Fanconi's syndrome. Case reports of lymphoproliferative disorders associated with paraproteinemia and Fanconi's syndrome suggest a somewhat better prognosis with this clinical entity.

To date, all "functioning" or "hot" tumors on salivary gland scan have been benign - either the not uncommon Warthin's tumor or the rare oncocytoma. A positive salivary scan was obtained in a functioning malignant tumor of the parotid gland (a mucous-producing papillary adenocarcinoma). This occurrence has not previously been reported. The pathologic findings and the radionuclide images are demonstrated in this elderly female. It is presumed that the Technetium Tc99m pertechnetate has been concentrated in the tumor. The functioning epithelial cell, however, is not the benign oncocyte associated with other previously reported benign functioning tumors. Clinical discretion is therefore suggested in interpreting the significance of a functioning salivary gland tumor if encountered in an elderly female.

A fatal human infection with mesocercafiae of Alaria americana is described. Several thousand mesocercariae were estimated to be present in the peritoneal cavity, bronchial aspirate, brain, heart, kidney, liver, lungs, lymph nodes, pancreas, retroperitoneal adipose tissue, spinal cord, spleen, and stomach. Nine days from the onset of symptoms death resulted from asphyxiation due to extensive pulmonary hemorrhage probably caused by immun-mediated mechanisms. Circumstances suggest the victim probably ate inadequately cooked frog legs while hiking. Mesocercariae penetrated through the stomach wall and spread to the various organs both directly and via and circulatory system.