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Biomedical subjects

D Rosen

Publications and source records attributed to D Rosen.

At least 91 records · Page 5Linked to original sources

Morphometry of bladder carcinoma: definition of a new variable.

In this study two measurements of nuclear size, the mean area and the size distribution curve of nuclear area, were used to differentiate between two polar groups: nuclei from non-neoplastic urothelium and nuclei from transitional cell carcinomas of bladder with a poor clinical outcome. Wide separation of these groups is necessary if a measurement is to be used to assess tumour grade where the morphometric differences are intermediate between such polar groupings. Separation between two groups was best achieved using a weighted distribution of nuclear size and this is a means of objective scoring of urothelial tumours.

Carcinoma, Transitional Cell↗

Outcomes of care in birth centers. The National Birth Center Study.

We studied 11,814 women admitted for labor and delivery to 84 free-standing birth centers in the United States and followed their course and that of their infants through delivery or transfer to a hospital and for at least four weeks thereafter. The women were at lower-than-average risk of a poor outcome of pregnancy, according to many but not all of the recognized demographic and behavioral risk factors. Among the women, 70.7 percent had only minor complications or none; 7.9 percent had serious emergency complications during labor and delivery or soon thereafter, such as thick meconium or severe shoulder dystocia. One woman in six (15.8 percent) was transferred to a hospital; 2.4 percent had emergency transfers. Twenty-nine percent of nulliparous women and only 7 percent of parous women were transferred, but the frequency of emergency transfers was the same. The rate of cesarean section was 4.4 percent. There were no maternal deaths. The overall intrapartum and neonatal mortality rate was 1.3 per 1000 births. The rates of infant mortality and low Apgar scores were similar to those reported in large studies of low-risk hospital births. We conclude that birth centers offer a safe and acceptable alternative to hospital confinement for selected pregnant women, particularly those who have previously had children, and that such care leads to relatively few cesarean sections.

Adolescent↗

Advanced primary ovarian carcinoma in pregnancy.

A case of advanced ovarian carcinoma in pregnancy is described. The entity is usually difficult to diagnose; when it does occur, the objective should be to optimize both fetal and maternal outcome.

Adult↗

Perforated adenocarcinoma of the colon during pregnancy.

Performated carcinoma of the colon in pregnant women is a rare event. Only six cases have been reported in the literature, all except one in the recto-sigmoid. We present a case of perforated adenocarcinoma of the colon located above the peritoneal reflection and discuss the problem of diagnosis and management.

Adenocarcinoma↗

Acoustic and plasma guided lasertripsy (APGL) of urinary calculi.

The feasibility of using pulsed laser generated acoustic and plasma optical emission signals to monitor laser fragmentation of urinary stones was studied in vitro. A flashlamp pumped tunable dye laser operating at a wavelength of 504 nm. (coumarin green) was used as the laser source. Acoustic signals were recorded with a hydrophone which has a useful frequency response of up to 350 KHz. Plasma optical emissions were transmitted retrograde along the laser fiber and reflected through a beam splitter to an optical detection system consisting of a series of spectral filters (to transmit plasma radiation from 380 nm.-440 nm. and block any 504 nm. laser light) and a photomultiplier tube. Measurements of acoustic and plasma signals were taken from different urinary calculi, guidewires, catheters, blood, blood clots, bruised soft tissue and normal ureter. Signals were also obtained from stones placed in ureter of an ex vivo bovine urinary tract specimen. Results of monitoring both plasma and acoustic signals show that it is possible to determine, without direct vision, whether the laser is hitting stone, ureteral wall or lumen. Strong plasma and strong acoustic signals are produced by calculi; strong acoustic but no plasma signals suggest that the laser is hitting blood clot or bruised ureteral wall. Absent plasma and acoustic response indicate that the laser is discharging on normal ureter or in the lumen. These distinctions may allow clinical stone fragmentation without direct ureteroscopic vision.

Acoustics↗

Highly lytic in vivo primed cytolytic T lymphocytes devoid of lytic granules and BLT-esterase activity acquire these constituents in the presence of T cell growth factors upon blast transformation in vitro.

Demonstration of C-like "rings," lytic granules, and the Ca2+-dependent lytic proteins--perforin/cytolysin--thereof, in certain cytocidal lymphocytes has led to the hypothesis of a mechanism of lytic granule-exocytosis and a common terminal lytic step in lymphocyte and C-induced lysis. However, neither cytolytic granules, nor formation of C-like rings during lysis have been detected in mature, highly potent, peritoneal exudate CTL (PEL) derived directly from the site of allograft rejection or in cytocidal hybridomas derived from them (PEL hybridomas). We now report that when stimulated in vitro in the presence of Con A supernatant, as a source of T cell growth factors (TCGF) or rIL-2, small in vivo primed PEL transform into large, dividing cytolytic T cells (PEL blasts) that express the same lytic specificity of the original PEL in short term lytic assays. The PEL blasts, in contrast to PEL, possess massive quantities of lytic granules, and protease (N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester esterase) (BLT-esterase) activity as well as non-specific, cell-mediated cytolytic activity in a long term (4-h) assay. These results suggest that the proposed lytic mechanism involving exocytosis of lytic granules, perforin, and BLT-esterases and the formation of 10 to 20-nm lesions may apply to lysis induced by granule-containing effectors such as large granular lymphocytes and TCGF-dependent CTL lines, such as PEL blasts. However, killing by mature, in vivo primed CTL, such as PEL or their hybridomas, appears to be effected through an alternative, contact-induced, self-destruction process(es) of the target not involving secretory lytic granules or the above lesions. Hence, although the expression of lytic granules and BLT-esterase activities in cytolytic lymphocytes devoid of these components is induced by TCGF, these cellular constituents are not necessary for the expression of CTL-mediated target cell lysis by mature effector cells.

Animals↗

Fentanyl uptake by the scimed membrane oxygenator.

With the initiation of cardiopulmonary bypass (CPB), using a membrane oxygenator, the drop in circulating fentanyl concentration is greater than can be attributed to dilution alone. This study examined the Scimed brand (2A-800) membrane oxygenator as a site of fentanyl binding. Initial experiments used an assembled CPB circuit. Subsequent dissection and analysis of the oxygenator revealed that the silicone-based membrane sheets were the primary site of fentanyl binding. The silicone-containing waterproof wrapper was also responsible for 1% to 2% of fentanyl binding. Binding of fentanyl to the Scimed membrane oxygenator occurs at a rapid rate and continues until the membrane has taken up 130 ng/cm2 of membrane surface area. The interaction is complete by 15 to 30 minutes if suprasaturated concentrations are used. Samples of membrane material with a surface area of 1 cm2 were also studied. Isolated membrane squares in a nonmoving prime solution required two hours for saturation at the same fentanyl concentrations as the intact membrane with circulating prime. Introduction of motion to the priming solution accelerated the rate of fentanyl binding by the isolated membrane squares to a rate similar to the intact membrane. Motion also provided results similar to those previously reported using different analysis techniques. Therefore, this method of studying fentanyl-membrane interactions using samples of membrane and tritiated fentanyl is a valid model for the intact membrane oxygenator in the assembled bypass circuit. In addition to solution movement, fentanyl concentration of the priming solution was also found to affect the rate of fentanyl uptake. When fentanyl concentrations were used which were insufficient to achieve saturation of the membrane (10 ng/mL and 20 ng/mL), the rate of uptake was slowed. Binding of all available fentanyl under these conditions occurred within three hours. There is potential modification of this interaction by several clinically relevant factors, including temperature, pH, protein content of prime solution, and other drugs. These areas require further study before the saturation data are applied to clinical practice.

Absorption↗

Urine production and bladder function in fetuses with open spina bifida.

Hourly fetal urine production rate (HFUPR) and bladder filling and voiding were determined by real-time ultrasonography in 13 fetuses with open spina bifida (OSB) and compared with those of 101 normal fetuses from uncomplicated pregnancies at 16-40 weeks gestation. In normal pregnancy, the fetal bladder volume increases linearly with time and then decreases rapidly with micturition. The mean cycle length does not change significantly with gestation but both the mean bladder volume and HFUPR increase. In fetuses with OSB, ultrasonographic examination has demonstrated deviations from normal in both bladder filling and bladder emptying.

Female↗

Morphometry of bladder carcinoma: I. The automatic delineation of urothelial nuclei in tissue sections using an IBAS II image array processor.

Semi-automatic methods of morphometry require the boundaries of the objects under study to be drawn by hand. This is slow, tedious and does not guarantee accuracy. Complete automation, with recognition, detection and verification by computer is not yet feasible. Automatic detection of nuclear boundaries with observer verification provides a means of obtaining large amounts of data for analysis, quickly and with similar accuracy to manual tracing.

Cell Nucleus↗

Are lytic granules and perforin 1 involved in lysis induced by in vivo-primed peritoneal exudate cytolytic T lymphocytes?

We examined whether in vivo-primed, alloimmune, peritoneal exudate CTL obtained directly from the animal kill TC by perforating their membranes with C-like lesions produced by P1 or P2 originating in cytolytic granules of the CTL. In control experiments lytic granules were isolated from the formerly lytic CTLL-2 line as well as from Con A-activated lymphoblasts but not from the in vivo-primed CTL. The use of anti-P1 of CTLL-2 origin supports the above results in that immunoblots were positive with CTLL-2 extracts and isolated granules thereof but negative with extracts and isolated (nonlytic) granules from in vivo primed CTL; immunofluorescence of permeabilized cells gave similar results. We observed typical "ring structures" on EL4 membranes attacked by Ab + C as well as after exposure to lytic granules extracted from the formerly lytic CTLL-2 line; however, no such "structures" were observed after attack by the in vivo-primed CTL. These results are at variance with the recent suggestion of a common lytic mechanism--employed by CTL--of secreted lytic granules containing P1 (and P2) thereof that acts analogously to C9. An alternative mechanism for CTL-induced lysis not involving initial perforation of the TC membrane by 160A "holes" (Poly P1) has been presented elsewhere. It is important to note that our results with in vivo-primed CTL do not preclude involvement of a secreted, pore (channel)-forming agent(s) that is not observed by negative staining EM.

Animals↗

Maturation of cytolytic T lymphocytes.

We have studied the maturation of cytotoxic T-lymphocytes (CTL) following primary and anamnestic responses in vivo and in vitro. Parameters evaluated included: frequency of effector CTL, specificity of binding to and lysis of target cells, killing and recycling ability of individual CTL, and the avidity of effector-target conjugation. While the frequency of effector CTL in the peritoneal cavity of BALB/c mice immunized against leukemia EL4 of C57BL/6 origin increases from 0 to 35% in 11 days of priming, a paradoxically lower frequency has been observed usually after 2 degrees and repeatedly after 3 degrees immunizations both in the peritoneal cavity and in the spleen. The H-2 haplotype and H-2 sub-loci specificity of CTL is preserved upon repeated immunizations. Likewise, the rate of killing and recycling of individual CTL do not change throughout immunizations, suggesting that the cytolytic activity of individual effector CTL is discrete ("quantal") and not subject to maturation upon repeated immunizations. On the other hand, inhibition of conjugate formation and of lysis by antibodies against target major histocompatibility complex (MHC) or effector Lyt-2 determinants is consistently less effective with 3 degrees CTL, suggesting an increase in avidity of effector/target interaction upon repeated immunizations. A striking increase in apparent avidity has been observed during CTL priming in mixed lymphocyte reaction, as deduced from blocking by target cell MHC antibodies. These results suggest that alloimmune CTL undergo maturation with respect to their ability to interact with the target, and that the composition of the responding population is subject to moderate selective processes driven by repeated antigenic stimuli.

Animals↗

The use of interstitial radiation therapy in the treatment of persistent, localized, and unresectable cancer in children.

Two children with cancer that persisted after multiple exploratory laparotomies, external beam radiation therapy, and multidrug chemotherapy had gold 198 (198Au) seeds implanted into their localized but unresectable tumor. Both children are alive, are receiving no therapy, and are disease-free more than 2 years later. These two cases indicate the value of interstitial implant therapy in the treatment of some children with cancer.

Abdominal Neoplasms↗

Preparation of young red cells for transfusion using the Fenwal CS 3000 cell separator.

A pheresis procedure was devised to isolate young red cells by centrifugation using the Fenwal CS 3000 continuous flow cell separator. Young red cell enriched products were collected in a 2.5-3-hour procedure. Large numbers of white cells and platelets were collected with the red cells, but cryopreservation and subsequent washing removed 99% of the contaminating cells. At the completion of all processing a product yielding 70% of the total hemoglobin content of a standard frozen/deglycerolized red cell unit was produced. Autologous radiochromium survival of young red cells, measured in 12 normal donors, showed an average 24-hour recovery of 89.9% with a T50Cr of 40.8 days. In paired autologous studies (N = 4) there was a mean increase of 35% in the observed T50Cr of young red cells as compared to standard frozen red cells.

Blood Preservation↗

Interaction of cytochrome c with reaction centers of Rhodopseudomonas sphaeroides R-26: localization of the binding site by chemical cross-linking and immunochemical studies.

The location of the cytochrome binding site on the reaction center of Rhodopseudomonas sphaeroides was studied by two different approaches. In one, cross-linking agents, principally dithiobis(propionimidate) and dimethyl suberimidate, were used to link cytochrome c and cytochrome c2 to reaction centers; in the other, the inhibition of electron transfer by antibodies against the subunits was investigated. Cytochrome c (horse) cross-linked to the L and M subunits, whereas cytochrome c2 (R. sphaeroides) cross-linked only to the L subunit. The cross-linked reaction center-cytochrome complexes were isolated by affinity chromatography. The rate of electron transfer in the cross-linked cytochrome c2 complex was the same as that in the un-cross-linked complex. However, when cytochrome c was used, the rate in the cross-linked complex was about 15 times slower than that in the un-cross-linked complex. Fab fragments of antibodies specific against the L and M subunits blocked electron transfer from both cytochrome c (horse) and cytochrome c2 (R. sphaeroides). Antibodies specific for the H subunit did not block either reaction. We conclude that the cytochrome binding site on the reaction center is close (approximately 10 A) to both the L and M subunits, possibly in a cleft between them.

Binding Sites↗

Treatment of thrombotic thrombocytopenic purpura. Evaluation of plasma exchange and review of the literature.

This report examines the results of treatment in 21 patients with thrombotic thrombocytopenic purpura (TTP) diagnosed over a 4-year time period (1976-1980) with a review of the possible role of each form of therapy in relationship to the various proposed pathogenic mechanisms. There was a 76.2% (16/21) overall survival with no significant difference in initial hematologic values in patients not surviving. Patients not surviving did not achieve a sustained platelet count greater than 150,000/microliters at any time during their clinical course. 16 patients received steroids, antiplatelet agents and plasma exchange, with a total volume exchanged ranging from 20.8 to 1,455 ml/kg, as part of their treatment protocol. In this group of patients there was an 81.2% (13/16) survival, with 4 patients receiving additional therapy including splenectomy and/or vincristine. There was no correlation between the intensity of plasma exchange and the time to hematologic recovery. It is apparent that controlled clinical trials are necessary to better define the effectiveness of the present forms of therapy.

Adult↗

T lymphocyte-mediated cytolysis. III. Delineation of mechanisms whereby mitogenic and non-mitogenic lectins mediate lymphocyte-target interaction.

We have investigated the mechanism(s) by which mitogenic (concanavalin A [Con A], phytohaemagglutinin [PHA] and Lens culinaris agglutinin [LCA]) and non-mitogenic (soybean agglutinin, peanut agglutinin, wheat-germ agglutinin and pokeweed mitogen) lectins mediate, non-specifically, lectin-dependent lymphocytotoxicity (LDCC). We show that non-mitogenic lectins are ineffective mediators of LDCC, due to their inability to mediate effective binding of effector cytotoxic T cells (EC) and target cells (TC), and not to their failure to 'activate' TC-bound EC, as proposed before. Evidence is presented that in LDCC Con A and PHA exert their primary effect(s) by affecting the TC rather than the EC. Although the lectin LCA, unlike Con A and PHA, is equally reactive with either EC or TC, a direct comparison is difficult since the presence of LCA, but not Con A or PHA, during the entire assay is required for optimal kill. Furthermore, all three LDCC-supportive lectins (PHA, Con A and LCA) show a similar TC preference when tested in a EC-TC conjugation assay. Taken together, these results are inconsistent with the theory that lectins mediate LDCC by 'bridging' EC and TC through lectin-binding receptors followed by 'activation' of the TC-bound EC. We would like to suggest that the potential of mitogenic lectins to mediate EC-TC interaction is related to their modification of TC-surface constituents, possibly major histocompatibility complex determinants, rendering them recognizable, non-specifically by EC.

Animals↗