[Acquired hemophilia].
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Antineoplastic Agents↗
Biomedical subjects
R Kantor
Publications and source records attributed to R Kantor.
Acquired hemophilia masked by warfarin therapy.
People without hemophilia but with autoantibodies specifically directed against the procoagulant activity of factor VIII are known to have acquired hemophilia. The bleeding diathesis in these patients is often severe and life-threatening. The definite laboratory diagnosis of this disorder includes demonstration of low factor VIII levels in plasma with a high titer of factor VIII inhibitors, but the initial suspicion for its presence should rise in view of a prolonged partial thromboblastin time (PTT) and a normal prothrombin time associated with an acquired bleeding disorder. Oral anticoagulant treatment is known to prolong PTT as well, and the merger of these 2 situations may cause delayed diagnosis of acquired hemophilia with devastating consequences. We describe here the first reported case of acquired hemophilia diagnosed in a patient treated with warfarin. In such patients prolonged PTT may be ascribed to warfarin therapy rather than to acquired hemophilia, thus causing a dangerous delay in diagnosis.
Aged↗
Kaposi's sarcoma after lung transplantation in a Sephardic Jewish woman.
One of the four types of Kaposi's sarcoma (KS), KS after organ transplantation under immunosuppression, is a well-known entity and has been abundantly described in renal, heart and liver recipients. We report the second case of cutaneous KS after lung transplantation, under regular immunosuppression, in a Sephardic Jewish woman. This case, when added to the other 10 cases of posttransplantation KS reported from Israel, all being Sephardic Jews, indicates that in Israel, Sephardic Jews are at higher risk than Ashkenazi Jews to develop posttransplantation KS. This observation should be added to the well-known increased risk of Ashkenazi Jews to develop classic KS. Moreover, in Israel Ashkenazi Jews develop classic KS at higher rates than Sephardic Jews. This apparent discrepancy in the ethnic distribution between Sephardic and Ashkenazi Jews in classic versus posttransplantation KS may shed light on the pathogenesis of KS in general.
Female↗
[High alkaline phosphatase in subacute thyroiditis].
Subacute thyroiditis may be hard to diagnose, therefore patients are sometimes misdiagnosed and subjected to unnecessary work-up. We report a 37-year-old man with subacute thyroiditis and a high concentration of serum alkaline phosphatase. After aspirin treatment there was clinical improvement and decrease in rapid ESR, and in high serum thyroxin and alkaline phosphatase. The increased alkaline phosphatase, seen in as many as 50% of patients, is of hepatic origin, and is not caused by high serum thyroxin. Awareness of this relationship may help in diagnosis and may prevent unnecessary diagnostic procedures, which may be invasive.
Adult↗
Distribution of the CCR5 gene 32-base pair deletion in Israeli ethnic groups.
The discovery of inhibition of HIV-1 by selected chemokines and their receptors instills hope in AIDS researchers, especially because a 32-bp deletion in the chemokine receptor CCR5 (delta32-CCR5) provides resistance to HIV infection. A recent report found that the highest delta32-CCR5 frequency is among Ashkenazi Jews (20.93%). In the present study, we have determined by PCR the allelic frequency of delta32-CCR5 in 520 individuals representing a spectrum of ethnic groups living in Israel. The samples were obtained from the Israeli National Laboratory of Genetic Diversity. Our results showed that Ashkenazi Jews, as to be expected, have the highest frequency (10.19%), yet not significantly higher than that which has been reported for whites of European decent. Other ethnic groups, North African Jews, non-Jews, Middle Eastern Jews, and Ethiopian Jews, gave allelic frequencies of 2.08, 1.35, 1.15, and 0, respectively. Thus, the delta32-CCR5 mutation is found in Jews with the same allelic frequency as that found for residents of their countries of origin. Therefore, it appears that the delta32-CCR5 allele has been introduced into Jewish communities world wide through intermarriage and genetic drift.
Adult↗
Case of the month. A lump in the abdomen.
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Abdominal Pain↗
Automated high resolution optical mapping using arrayed, fluid-fixed DNA molecules.
New mapping approaches construct ordered restriction maps from fluorescence microscope images of individual, endonuclease-digested DNA molecules. In optical mapping, molecules are elongated and fixed onto derivatized glass surfaces, preserving biochemical accessibility and fragment order after enzymatic digestion. Measurements of relative fluorescence intensity and apparent length determine the sizes of restriction fragments, enabling ordered map construction without electrophoretic analysis. The optical mapping system reported here is based on our physical characterization of an effect using fluid flows developed within tiny, evaporating droplets to elongate and fix DNA molecules onto derivatized surfaces. Such evaporation-driven molecular fixation produces well elongated molecules accessible to restriction endonucleases, and notably, DNA polymerase I. We then developed the robotic means to grid DNA spots in well defined arrays that are digested and analyzed in parallel. To effectively harness this effect for high-throughput genome mapping, we developed: (i) machine vision and automatic image acquisition techniques to work with fixed, digested molecules within gridded samples, and (ii) Bayesian inference approaches that are used to analyze machine vision data, automatically producing high-resolution restriction maps from images of individual DNA molecules. The aggregate significance of this work is the development of an integrated system for mapping small insert clones allowing biochemical data obtained from engineered ensembles of individual molecules to be automatically accumulated and analyzed for map construction. These approaches are sufficiently general for varied biochemical analyses of individual molecules using statistically meaningful population sizes.
Animals↗
Orthopaedic long term aspects of bladder exstrophy.
This study evaluates long term orthopaedic aspects of children with bladder exstrophy who were operated on using different techniques and at different ages. Data were accumulated from 20 patients with an age range of 2 to 29 years (average, 13 years). Fourteen patients underwent pelvic osteotomy. Interviews and physical examinations confirmed that, in the long term, children with classical bladder exstrophy do not have significant orthopaedic problems or disability, whether or not they underwent pelvic osteotomy. Radiographic imaging showed normal hip joint configuration with marked pubic diastasis. There were no clinical problems associated with the diastasis. Pelvic computed tomography studies in 7 patients showed marked remodeling of the femora and acetabula. Radiographs of the spine showed a curve in 7 (47%) of the patients, but in only 3 cases was the curve larger than 10 degrees. Pelvic osteotomy is indicated during surgical correction of bladder exstrophy to facilitate closure of the abdominal wall to prevent postoperative wound dehiscence and possibly achieve better urinary control in older age. However, there is no clear indication for pelvic osteotomy from an orthopaedic point of view.
Adolescent↗
Adults' knowledge about the use of child restraint devices.
BACKGROUND: Injuries are the number one cause of morbidity and mortality among children age 14 and younger in the United States, and motor vehicle crashes account for most of these injuries. Although child restraint devices (CRDs) have been shown to protect children involved in motor vehicle crashes, only minimal decreases in mortality and morbidity have occurred since their introduction. This study evaluated the accuracy and sources of adult knowledge about CRDs. METHODS: A self-administered questionnaire was completed by patients at a community-based family practice clinic to obtain demographic information, assess knowledge of recommendations for CRD use, and identify sources of this knowledge. RESULTS: Of the 368 participants, 36% were men, 52% were women, and 12% did not indicate gender. The frequencies of correct responses on positioning infants younger than nine months of age and weighing less than 20 lbs in a CRD were: upright, 47%; rear middle-seat location, 22%; and rear facing, 54%. For toddlers older than nine months who weighed more than 20 lbs, the frequencies of correct responses on positioning were: using a booster seat plus a seat belt, 71%; rear-middle location, 17%; and front facing, 66%. In addition, only 42% of the respondents correctly identified the booster seat as not crash-test certified, and 44% indicated that a CRD should not be reused after an accident. The majority of respondents indicated that the year of manufacture was important and that loose objects in the car were not safe. TV/radio (51%), newspaper/magazine (41%), and relatives (31%) were the most common sources of information about CRD use. CONCLUSION: Our findings suggest that a lack of knowledge about CRD use among adults contributes to improper use of these devices. This may explain the minimal effect CRD use has had on reducing morbidity and mortality of children from motor vehicle crashes.
Accidents, Traffic↗
Analysis of rat natural killer cytotoxic factor (NKCF) produced by rat NK cell lines and the production of a murine monoclonal antibody that neutralizes NKCF.
Natural killer cytotoxic factor (NKCF) is produced as a result of the interaction of murine, rat, or human natural killer (NK) cells with NK-susceptible targets. This factor has been linked to the target cell lysis mediated by the NK effector cell. In the present results, culture supernatants from rat large granular lymphocyte (LGL) tumors exhibited NKCF activity which lysed the susceptible targets, MBL-2 and YAC-1. NKCF production from these rat tumor lines was spontaneous and was not significantly increased by co-incubation of the LGL tumors with target cells, target cell membranes, or by preincubation of the LGL tumor cells with interferon or interleukin 2. In addition to NKCF activity, the supernatants lysed L929, indicating the presence of tumor necrosis factor (TNF) in these preparations. The presence of this latter cytokine was verified using specific antibodies to recombinant murine TNF which neutralized the L929 activity while not affecting the NKCF activity against MBL-2 or YAC-1. Mouse monoclonal antibodies (mAb) A0287, A0462, and A0316) which significantly inhibit the NKCF cytolytic activity of these LGL-derived supernatants were also produced. These antibodies were shown to cross-react with human NKCF in a manner similar to that seen in the rat. Interestingly these same mAb demonstrated no inhibition of L929 cytotoxicity from either LGL-derived supernatants or by recombinant murine or human TNF. To examine further the specificity of these antibodies, they were chemically linked to Sepharose 4B and found to remove a significant proportion of the NKCF cytolytic activity from LGL supernatants, while not affecting the TNF reactivities in these preparations. In addition, these antibodies demonstrated significant inhibition of cell-mediated cytotoxicity by rat LGL against YAC-1 target cells. Biochemical analysis of labeled NKCF-containing supernatants indicated the major protein recognized by these anti-NKCF mAb to be approximately 12,000 m.w. The use of these mAb against NKCF should be very useful in further purification and biochemical characterization of NKCF and in studying its role in a variety of cell-mediated cytotoxicity assays.
Animals↗
Abnormal head and neck movements associated with esophageal perforation and abscess caused by an ingested foreign body.
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Abscess↗
Molecular heterogeneity and shedding of a high-molecular-mass melanoma-associated antigen identified with monoclonal antibodies.
This review briefly discusses some recent developments in the use of monoclonal antibodies to study antigens of high molecular mass associated with melanomas, including information on their molecular profile, their heterogeneity, and the effect of interferon on their shedding by melanoma cells.
Antibodies, Monoclonal↗
Preparation of fingernails for trace element analysis.
There are substantial differences in the reported elemental composition of human nails. Most investigators have used extensive washing procedures to minimize environmental contamination, however, such washing poses the risk of extraction of elements bound to the nail matrix. To determine if a portion of this variability could be accounted for by the "washing solutions" used by different investigators, nails were washed in nine solvents previously used for cleaning nails and their residual elemental composition measured by atomic absorption spectroscopy or energy dispersion analysis. In general, treatment with organic solvents resulted in less elemental loss than did treatment with aqueous detergents, while aqueous acids caused the greatest loss. Organic solvents more readily extracted iron and magnesium than calcium, copper and zinc. Virtually all of the magnesium was extracted by distilled water or aqueous detergents.
Calcium↗
Lymphocyte subpopulations in minimal change nephrotic syndrome.
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Adolescent↗
Studies of the normal human placental syncytiotrophoblast membrane: a combined immunological and physiochemical approach.
In view of the importance of the syncytiotrophoblast in the immunobiology of human pregnancy, the composition of this interface between fetus and mother was further studied by a combination of physicochemical and immunological approaches. Trophoblast membranes were solubilized using three classes of detergents: zwitterionic (sulfobetaine14), non-ionic (Triton X-100), and anionic (deoxycholate). Quantitative studies of protein released demonstrated the importance of dispersion of membranes into detergent, and optimum solubilization was then obtained at detergent:protein ratios of 1.3:1 for sulfobetaine, 2.5:1 for Triton X-100, and 4.4:1 for deoxycholate. Analysis of chaotrope-treated detergent-solubilized membrane components was performed by preparative isoelectric focusing followed by combined physiocochemical and immunological methods. The results revealed three major proteins which were identified as placental alkaline phosphatase, albumin, and transferrin. Certain additional low molecular weight proteins were also evident; one of these components displayed physicochemical properties similar to those of actin, but none appeared to be recognized by conventional heteroantisera raised to trophoblast membrane. These findings and the results of further immunological analysis by affinity chromatography are consistent with the concept that human trophoblast may express limited immunogenicity due in part to the presence of large amounts of absorbed maternal serum components and limited expression of fetal proteins.
Albumins↗
Prevalence of a CCR5 gene 32-bp deletion in an Israeli cohort of HIV-1-infected and uninfected hemophilia patients.
OBJECTIVE: The recently discovered connection of chemokines and their receptors to HIV pathogenesis, and the description of the 32-bp deletion in the CCR5 gene (delta 32 CCR5), led to heightened excitement and numerous reports regarding their role in HIV transmission and disease progression. The populations in most of these reports, except for one, consisted of homosexual men. Our objective was to investigate the significance of delta 32 CCR5 in hemophilia patients in Israel. STUDY DESIGN/METHODS: We have determined by polymerase chain reaction (PCR) the prevalence of delta 32 CCR5 in 34 HIV-seropositive Israeli patients with hemophilia A and compared them with a control group of 42 HIV-seronegative hemophilia patients. RESULTS: Thirteen heterozygotes were identified among the 76 hemophilia patients tested (allelic frequency, 8.5%), 5 (14.7%) among the HIV-seropositive patients, and 8 (19%) among the noninfected. CONCLUSIONS: No protective advantage to delta 32 CCR5 heterozygosity was seen as far as infection with HIV is concerned. However, a trend of a slower progression to AIDS in delta 32 CCR5 heterozygotes compared with wild-type homozygotes may be apparent, although no absolute correlation could be made.
Cohort Studies↗
[Monoclonal antibodies and uveal melanomas].
The authors, who have succeeded since 1976 in cultivating cells of ocular melanoma in continuous lines report the different stages for producing specific monoclonal antibodies. They particularly insist on the demonstration, through radioimmunoassay, of the specificity of marked monoclonal antibodies, on the immunohistochemical study and on biodistribution. From these data, an immunotherapy protocol has been perfected and starts being applied to human beings.
Animals↗