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Biomedical subjects

R Rabinowitz

Publications and source records attributed to R Rabinowitz.

At least 19 recordsLinked to original sources

Hyposialated 185 kDa CD45RA+ molecules attain a high concentration in B lymphoma cells and in activated human B cells.

Alternate splicing of exons of the CD45 molecule generates multiple isoforms differing in their molecular weights (MWs). In B-lymphocytes the CD45RA isoform was previously shown to be expressed on glycoproteins with MWs of 220 and 205 kDa, while the CD45RO isoform was expressed on glycoproteins with MW of 180 kDa. The present study demonstrated that B cell lymphomas and activated B-cells contain CD45 molecules with a MW of 185 kDa that express the CD45RA and CD45RC specificities but neither the CD45RB nor the CD45RO specificities. 185 kDa CD45RA+ molecules were detected in B cell lymphoma B lines, in Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines, and in tonsillar B cells, but not in normal, unstimulated peripheral blood B cells. These molecules were not detected in neoplastic and normal T cells. CD45RA+ 185 kDa molecules were present in B cells from three non-Hodgkin's patients in leukemic phase were not detected in B lymphocytes of seven of nine CLL patients tested. Trypsin treatment eliminated only 220 kDa CD45RA+ molecules but not 185 kDa CD45RA+ molecules, indicating that the 185 kDa CD45RA+ molecules are not expressed on the cell surface. Pulse-chase experiments, and studies on the effects of tunicamycin, neuraminidase and O-glycosidase, indicated that the 185 kDa molecules are partially glycosylated CD45RABC molecules that constitute precursors of the 220 kDa molecules. The high concentration of 185 kDa CD45RA+ molecules in B lymphoma cells and in activated B cells seems to reflect a high turnover of CD45RA+ molecules characteristic for these cells.

Antigens, Neoplasm↗

Autonomic dysfunction in experimental autoimmune neuritis: heart rate.

Autonomic nervous system (ANS) dysfunction occurs in more than half of Guillain--Barré syndrome (GBS) patients and is an important cause of death in the disease. In this study we examined heart rate (HR) changes in an animal model of GBS, experimental autoimmune neuritis (EAN), induced by immunization with myelin extracted from bovine spinal roots. The animals developed progressive motor weakness accompanied by significant weight loss and hypothermia. HR was measured in 33 EAN rats at rest (rHR) and followings stressful stimulation (sHR). Average pre-immunization rHR was 341+/-28 beats per minute (b.p.m.) and sHR was 486+/-21 bpm. Although the mean rHR in rats with EAN was not significantly different compared to that at baseline, there was a significant increase of variation of rHR with six rats demonstrating bradycardia (<280 b.p.m.) and 10 tachycardia (>400 b.p.m.) (P<0.01, F-test). sHR in EAN rats was significantly lower (P<0.01), suggesting sympathetic system impairment. These findings may serve as a basis for testing treatments of ANS dysfunction in EAN.

Animals↗

Does urinary tract ultrasonography at hospitalization for acute pyelonephritis predict vesicoureteral reflux?

PURPOSE: We evaluate the correlation between urinary tract ultrasound during hospitalization for acute pyelonephritis with subsequent voiding cystourethrography in children. MATERIALS AND METHODS: Medical records were reviewed of 184 children up to 18 years old who were evaluated with ultrasound during hospitalization for acute pyelonephritis between January 1988 and January 1996. Followup voiding cystourethrography results were compared to the initial ultrasound findings. RESULTS: Ultrasound was performed at mean hospital day 2.1 and voiding cystourethrography was done 39 days later. Of the ultrasound studies 77 (42%) were abnormal, and two-thirds of these abnormalities were upper tract dilatation. Subsequent voiding cystourethrography was performed in 76% of the study population, including 67% of those with normal and 87% of those with abnormal ultrasound. Voiding cystourethrography revealed reflux in 39% of children with upper tract dilatation compared to 35% of those with normal and 36% with abnormal ultrasound for any reason. In addition, the severity of reflux on voiding cystourethrography could not be predicted by ultrasound findings. CONCLUSIONS: Ultrasound findings during acute pyelonephritis do not correlate with and are not predictive of the presence or grade of vesicoureteral reflux on subsequent voiding cystourethrography.

Acute Disease↗

Suppressors of cancer cell proliferation from fig (Ficus carica) resin: isolation and structure elucidation.

A mixture of 6-O-acyl-beta-D-glucosyl-beta-sitosterols, the acyl moeity being primarily palmitoyl and linoleyl with minor amounts of stearyl and oleyl, has been isolated as a potent cytotoxic agent from fig (Ficuscarica) latex and soybeans. Identity was established by spectroscopic methods (NMR, MS) and confirmed by chemical synthesis. Both the natural and the synthetic compounds showed in vitro inhibitory effects on proliferation of various cancer cell lines.

Antineoplastic Agents, Phytogenic↗

Treatment of MRL/lpr mice, a genetic autoimmune model, with the Ras inhibitor, farnesylthiosalicylate (FTS).

Activation and proliferation of lymphocytes requires the active signal transducer Ras. Activation of lymphocytes, associated with autoimmunity, may therefore be modified by S-farnesylthiosalicylic acid (FTS), a synthetic substance that detaches Ras from the inner cell membrane and induces its rapid degradation. The MRL/lpr mouse is a genetic model of a generalized autoimmune disease sharing many features and organ pathology with systemic lupus erythematosus (SLE) and the primary antiphospholipid syndrome (APS). The objective of the present study was to examine the effect of FTS on laboratory and clinical pathology in the MRL/lpr mouse. Female MRL/lpr (n = 50) and MRL/++ control (n = 35) mice were treated intraperitoneally with either FTS (5 mg/kg/day) or saline between 6 and 18 weeks of age. The mice were weighed, tested for proteinuria and lymphadenopathy, lymphocyte proliferation, antibodies, grip strength and behaviour in an open field. FTS treatment resulted in a 50% decrease in splenocyte proliferation to ConA, LPS and a disease specific antigen, beta(2)-glycoprotein-I, and in a significant decrease in serum antibody levels against cardiolipin and dsDNA. Proteinuria and grip strength were normalized and lymphadenopathy and postmortem lymph node and spleen weights were significantly reduced in FTS treated MRL/lpr mice. These findings indicate that modulation of Ras activation has a significant impact on the MRL/lpr model and may represent a new therapeutic approach for the treatment of systemic autoimmune diseases such as SLE and APS.

Animals↗

Regulation of the expression of CD45 isoforms in the Farage human B cell lymphoma line and its 10.6.1 subline.

Different B-cell neoplasias vary in the expression of CD45 isoforms. In the present study two sublines of a human B cell lymphoma- the original Farage line (Farage OL) and the Farage 10.6.1 subline were used to analyze the regulation of the expression of CD45 cell surface determinants. Cells of the Farage OL line constitutively expressed both CD45RO and CD45RA determinants on their cell surface. In contrast, the majority of the cells of the Farage 10.6.1 subline expressed CD45RA, and only few cells were CD45RO+. The low molecular spliced CD45 mRNA, characteristic for CD45RO was found in Farage OL cells, but was almost undetectable in Farage 10.6.1 cells. Following exposure to interleukin-4 (IL-4) a large proportion of the Farage 10.6.1 cells expressed CD45RO while in Farage OL cells the proportion of CD45RO+ was slightly reduced. The low molecular, spliced mRNA characteristic for CD45RO, was increased in Farage 10.6.1 cells following IL4 stimulation, but was slightly reduced in Farage OL cells. The molecular weight of CD45RA molecules produced by Farage cells varied from 185 kDa to 220 kDa while that of CD45RO molecules was 175 kDa. Preliminary attempts were made to determine a possible correlation between the expression of CD45RO and apoptosis in Farage cells. In both the Farage OL and Farage 10.6.1 cells the proportion of Bcl-2+ cells was lower among CD45RO+ cells than among CD45RO- cells. The present study indicates that IL4 has different effects on the alternative splicing of CD45 mRNA in two closely related B cell lymphoma lines. Thus, factors produced by the B lymphoma cells themselves may endow the cells with different patterns of responsiveness to a single stimulatory agent.

Blotting, Western↗

B-lymphocytes in CLL and NHL differ in the mRNA splicing pattern of the CD45 molecule.

In the present study the cell surface expression of CD45 isoforms on normal and neoplastic human B cells was correlated with splice products of the CD45 mRNA, using RT-PCR technology. In non-Hodgkin's lymphoma cells in the leukemic phase (NHL) the majority of the cells expressed a high level of CD45RA, while in CLL most of the cells expressed a low level. In the Raji and Daudi Burkitt B-cell lymphoma lines the main CD45 mRNA product was the largest, unspliced, full-length isoform (456) and the 56 splice product. Similar results were obtained with B-cell lymphoma cells isolated from the peripheral blood of patients with NHL in the leukemic phase. In EBV-transformed B-cell lines, the 456 and the 56 isoform of CD45 mRNA were predominant, but in addition a low level of the 5- and 0-exon splice products was detected. A strikingly different pattern was obtained with B-CLL cells. In CLL the level of the 456 and the 56 isoforms was low, while that of the 5- and 0-exon splice products was increased. Thus, in contrast to the heterogeneity in the expression of CD45RO in B-CLL, the majority of the cells contained the CD45 mRNA splice product coding for CD45RO. Analysis of splice products of the CD45 mRNA may serve as an additional tool to differentiate CLL from the leukemic phase of NHL.

B-Lymphocytes↗

Natural killer (NK) and T cell-associated surface marker expression following allogeneic and autologous bone marrow transplantation (BMT).

Natural killer (NK) and T cell development was studied after allogeneic and autologous BMT. We determined the phenotypic expression and lytic ability of these subpopulations after BMT. Following T cell-depleted (TCD) BMT, the number of CD16+ and CD56+ cells peaked at 39 and 46 days, respectively, and constituted the majority of peripheral blood lymphocytes (PBL). Coexpression of CD3 and CD16 was <10% up to 14.5 weeks after transplant. Following allogeneic non-T cell-depleted (NTCD) BMT, the number of CD16+ and CD56+ cells peaked at 6 weeks. CD3 expression was normal (70%-80%), % CD8+ cells was high (40%), and % CD4+ cells was low (20%). Following autologous BMT (ABMT), % CD3+ T cells was 80%, of which 70% expressed the CD8 marker. In contrast, CD4 expression was low (20%). CD16+ cells appeared 2.5-3 weeks after ABMT but with low frequency (20%), at which point 20%-30% of the CD3+ cells coexpressed CD16. A positive correlation was found between CD16 expression and cytotoxic capability. In conclusion, a marked difference was observed in NK and T cell-associated markers following TCD BMT, NTCD BMT, and ABMT. Following NTCD or ABMT, but not TCD BMT, a high percentage of cells co-express CD16 and CD3, which may indicate the possibility of a common NK and T cell progenitor.

Adolescent↗

Minimally invasive treatment for localized adenocarcinoma of the prostate: review of 1048 patients treated with ultrasound-guided palladium-103 brachytherapy.

PURPOSE: To assess the effectiveness of palladium-103 brachytherapy in stage T1 and T2 adenocarcinoma of the prostate. PATIENTS AND METHODS: The charts of 1048 patients treated between 1991 and 1999 with transperineal realtime ultrasound-guided (103)Pd (Theraseed) implants were reviewed to assess the effects on serum prostate specific antigen (PSA) values and tissue (biopsy). Of the 1048 patients, 780 had sufficient data for this report. Preoperative total androgen blockade (leuprolide and flutamide) was used selectively in patients whose prostate size was >50 cc and those whose tumors had a Gleason score of >7. RESULTS: At 1 year, 86% of the evaluable 766 patients had stable PSA concentration <1.5 ng/mL; at 5 years, 86% of the 166 patients with data available had stable PSA values <1.5 ng/mL. Biopsies were negative in 92% of the patients studied at 2 years. Patients with pretreatment PSA values <10 ng/mL had the best outcomes, and those treated with (103)Pd plus hormone ablation achieved PSA reduction more rapidly than those treated with radioisotope monotherapy. There was one disease-related death; the principal morbidity was short-term bladder and bowel irritation without permanent sequelae. Impotence occurred in approximately 15% of patients, and incontinence occurred in 5% of those who had undergone prior transurethral resection of the prostate. CONCLUSION: The technique used in this study proved effective in reducing PSA concentrations to <1.5 ng/mL and in producing negative biopsies 1 and 2 years postoperatively. These results are comparable to those of external-beam radiation therapy and radical prostatectomy while demonstrating a significant reduction in morbidity.

Adenocarcinoma↗

Evolution of techniques for ultrasound-guided palladium 103 brachytherapy in 950 patients with prostate cancer.

PURPOSE: Brachytherapy is an effective, low-morbidity, cost-effective treatment for adenocarcinoma of the prostate. Although both iodine 125 and palladium 103 have been used extensively over the last 14 years, 103Pd (Theraseed) provides a more rapid initial dose and therefore better control of higher Gleason grade tumors. We assessed a highly refined methodology for 103Pd brachytherapy in patients with prostate cancer and compared outcomes before and after making adjustments in technique. MATERIALS AND METHODS: Standard brachytherapy techniques were modified to include combination of preplanning with real-time adjustment, placing all needles at once to minimize prostate movement, using monitored anesthesia control sedation during preoperative volume study and cystoscopy, and several other small but important changes. Charts were reviewed from 950 patients treated with 103Pd implants from 1991 through 1999. Prostate-specific antigen (PSA) and biopsy data before and after 1993 were compared for 733 patients whose data qualified for analysis. RESULTS: At 1 and 5 years after treatment, 85-88% of patients had stable PSA <1.5 ng/mL. Biopsies were negative in 90-94% at 2 years. CONCLUSION: The modification in techniques provides positive results that remain stable over time.

Adenocarcinoma↗

Detection of minimal residual disease (MRD) after bone marrow transplantation (BMT) by multi-parameter flow cytometry (MPFC).

Multi-parameter flow cytometry (MPFC) was used to detect minimal residual disease (MRD) following bone marrow transplantation (BMT) in 21 patients. Bone marrow (BM)was analyzed pre-transplant and 3-4 months post-BMT while the patients were in clinical and morphological remission. MRD was detected by identifying cells with aberrant antigen expression and/or leukemia-associated phenotype (LAP) using MPFC. Prior to BMT, 8 out of 21 patients exhibited normal antigen expression based on normal BM samples while 13 BM aspirates had abnormal MPFC. Pre-BMT MPFC was abnormal in all 10 patients who were not in complete remission (CR) (>5% blasts in BM) as well as 3 patients acute lymphoblastic leukemia (ALL) who were in CR. In BM from ALL patients, an abnormal uniform B cell population was observed however antigen expression patterns varied greatly between patients. BM from acute myeloblastic leukemia (AML) patients showed an abnormal distribution of CD34+ cells. In addition, a correlation was observed between pre-BMT cytogenetics and MPFC. Only 2 out of 8 (25%) patients with normal MPFC pre-autologous bone marrow transplantation (ABMT) relapsed (AML), while 6 out of 13 (46%) patients with abnormal pre-BMT MPFC relapsed including 2 out of 3 patients who were transplanted in clinical CR. Pre-BMT MPFC may thus be an effective tool for detection of MRD by detection of a pre-transplant MPFC abnormality.

Adolescent↗

Monocytes confer CD14 antigenicity on activated lymphocytes.

In the present study, exposure of human peripheral blood mononuclear cells (PBMC) to phorbol 12-myristate 13-acetate (PMA) was found to elicit the expression of CD14 on lymphocytes. Less than 3% of the lymphocytes present among freshly isolated PBMC were stained with 63D3 anti-CD14 monoclonal antibody (mAb). Within two days of exposure of PBMC to PMA, up to 30% of the lymphocytes reacted with the 63D3 anti-CD14 mAb, though not with the LeuM3 and My4 anti-CD14 mAbs. The appearance of CD14 on lymphocytes was also elicited by exposure of PBMC to phytohemagglutinin (PHA), concanavalin A (Con A), or agarose-bound phytohemagglutinin but not by exposure to lipopolysaccharide, interferon-alpha, or interleukin-2. Purified lymphocyte preparations did not acquire CD14 following stimulation with PMA. Monocytes lost their reactivity with CD14 mAbs (63D3, LeuM3, and My4) within a few hours after exposure to PMA. The level of soluble CD14 was higher in supernatant fluids of cultures of untreated PBMC than of PMA-stimulated PBMC. The addition of PMA to cultures of T cells and monocytes separated by Millipore filters lead to the expression of CD14 on the lymphocytes. The present study indicates that activation of lymphocytes in the presence of monocytes leads to the appearance of CD14 on lymphocytes, and raises the possibility that the expression of CD14 on lymphocytes may result from the transfer of CD14 molecules from monocytes to lymphocytes.

Cell Communication↗

360 Degrees of epibulbar granulation tissue thirteen years after silicone circle buckle operation.

To demonstrate a granulomatous reaction to silicone buckel thirteen years after retinal detachment surgery. We report on a 71-year-old man who developed a 360 degrees of epibulbar granulation tissue due to silicone circle buckel. The granulation tissue was demonstrated by a computer tomography and histologically. A granulomatous reaction to silicone circle buckel can be found many years from the first operation. Biopsy is always necessary to establish a definitive diagnosis. Treatment of 360 degrees of epibulbar granulation tissue causing ocular dysfunction is by surgical excision.

Aged↗

Lymphocyte subset profile of young healthy children residing in a rural area: possible role of recurrent gastrointestinal infections.

BACKGROUND: Lymphocyte subsets in healthy children are currently characterized by age-related standards. Because antigenic stimuli play a role in maturation of the immune system after birth, there is a question of whether cellular immune development differs in infants whose living conditions entail extensive antigenic exposure and infants growing up in a more protected environment. METHODS: Peripheral blood lymphocyte subsets were studied in two populations of children of similar age and nutritional status; children belonging to a rural population residing in proximity with farm animals and children from an economically privileged urban population. In each population, children studied included a group with an acute diarrheal episode and a healthy control group. RESULTS: Among rural population children, 65% had experienced at least one episode of gastroenteritis within the previous 3-month-period, compared with less than 10% of urban population children. In the rural population group 15% had experienced two or more episodes of gastroenteritis. The proportion of helper T cells was similar in rural population and urban population children. Among helper T cells, the proportion of CD29+ "memory" cells of the total CD4+ helper T cells was more than two times higher than those in rural population children. The proportion of CD8 cells was higher in rural population children than in urban population children, and the proportion of natural killer cells, CD56+ and CD57+, was two to three times higher in rural population children. Within each population, peripheral blood lymphocyte subsets did not differ between the healthy control group and those with acute diarrhea. CONCLUSIONS: In young children exposure to environmental pathogens and specifically to gastrointestinal antigenic stimuli is a major factor affecting development of the cellular immune response. Young children who have experienced enhanced infectious exposure have a peripheral blood lymphocyte profile similar to that of adults.

Acute Disease↗

Prenatal sonographic appearance of congenital fibrosarcoma.

Congenital fibrosarcoma is a rare soft tissue sarcoma. A 22-year-old woman in the 22nd week of her first pregnancy underwent sonographic examination, which revealed a soft tissue swelling of the fetus's left thigh. The pregnancy was terminated, and congenital fibrosarcoma was diagnosed by pathologic examination. To our knowledge, this is the first published report of the intrauterine sonographic observation of this tumor in a fetal extremity.

Adult↗

Ureteral valves in children.

OBJECTIVES: Congenital ureteral valves are a rare cause of ureteral obstruction in children, with only 42 cases having been reported in peer-reviewed literature. Eight additional cases of ureteral valves are herein reported. METHODS: We report on the diagnosis and management of eight children with ureteral obstruction secondary to a ureteral valve. RESULTS: Eight children with congenital ureteral valves were managed by ipsilateral ureteroureterostomy, ureteropyelostomy, or longitudinal ureterotomy with excision of valve leaflets. The obstruction was relieved in all. CONCLUSIONS: Ureteral valves should be included in the differential diagnosis of ureteral obstruction in children. Reconstruction is curative.

Adolescent↗