Fatal erythroderma associated with pentostatin.
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Antibiotics, Antineoplastic↗
Biomedical subjects
R Finney
Publications and source records attributed to R Finney.
Jumping translocation at 11q23 with MLL gene rearrangement and interstitial telomeric sequences.
myeloid leukemia of acute myeloid leukemia (AML) M5a showing a jumping translocation with a breakpoint at 11q23. Fluorescence in situ hybridization (FISH) demonstrated triplication of the MLL gene and the presence of interstitial telomeric sequences, supporting the role of repetitive sequences in the mechanism of jumping translocations. Southern blot analysis of the MLL breakpoint cluster region showed the presence of an MLL gene rearrangement. Jumping translocation with MLL gene rearrangement is a previously unreported phenomenon in leukemia cytogenetics.
Aged↗
Molecular remission in Philadelphia-positive adult acute lymphoblastic leukaemia rapidly induced by conventional-dose chemotherapy.
This report describes a patient presenting with Ph-positive ALL. RT-PCR analysis of diagnostic marrow revealed the presence of three bcr/abl transcripts; the ALL type ela2 along with the CML types, b2a2 and b3a2. After initial induction therapy, bcr/abl transcripts were only detectable after two rounds of PCR but after MIDAC consolidation, remission samples were two-round negative. The relationship between the unusual molecular biological profile of this leukaemia and the rapid attainment of molecular remission is discussed.
Adult↗
Endogenous natural killer enhancing factor-B increases cellular resistance to oxidative stresses.
Natural killer-enhancing factor (NKEF) was identified and cloned on the basis of its ability to increase NK cytotoxicity. Two genes, NKEF-A and -B, encode NKEF proteins and sequence analysis presented suggests that each belongs to a highly conserved family of antioxidants. To examine the antioxidant potential of NKEF, we transfected the coding region of NKEF-B cDNA into the human endothelial cell line ECV304. The stable transfectant, B/1, was found to overexpress NKEF-B gene transcript and protein. We subjected B/1 to oxidative stress by either culturing them with glucose oxidase (GO), which continuously generates hydrogen peroxide, or by direct addition of hydrogen peroxide. We found that B/1 cells were more resistant than control cell lines. Resistance to hydrogen peroxide was originally thought to be mediated mainly by catalase and the glutathione cycle. Therefore, we used inhibitors to block the two pathways and found that B/1 cells were more resistant to oxidative stress than control cells when we used inhibitors to preblock either pathway. We also examined the cellular inflammatory responses to oxidized low-density lipoprotein (LDL) and bacterial lipopolysaccharide (LPS) by measuring monocyte adhesion to endothelial cells in vitro and found that B/1 cells were resistant to such responses. Lastly, we found that B/1 cells were more resistant to a novel chemotherapeutic agent CT-2584, which appears to kill tumor cells by stimulating production of reactive oxygen intermediates in mitochondria. These results demonstrate that the NKEF-B is an antioxidant that protects cells from oxidative stress, chemotherapy agents, and inflammation-induced monocyte adhesion. Furthermore, its expression may mediate cellular responses to proinflammatory molecules.
Antioxidants↗
Detection of urinary incontinence during ambulatory monitoring of bladder function by a temperature-sensitive device.
OBJECTIVES: To determine whether the difference between urinary and perineal temperatures is sufficient to allow registration of incontinent episodes by detection of temperature change alone. To design and assess the use of a diode-based temperature-sensitive device in the detection of episodes of urinary incontinence in long-term ambulatory monitoring (LTAM) studies. SUBJECTS AND METHODS: Perineal temperature recordings were made in 46 women during various activities. A temperature-sensitive device consisting of six IN4148 diodes, spanning 5 cm, and a nearby reference negative diode, was placed in a light perineal pad and attached to a portable amplifier/digitizer and recorder. The performance of the device was determined by comparison with increases in pad weight in 51 incontinent and 23 continent control subjects. RESULTS: A sufficient temperature differential existed between perineal and urinary temperature during all activities except being seated with crossed legs. Incontinence was reliably detected by the temperature-sensitive device. The device had a sensitivity of 95.2% and a specificity of 90.6% compared to a pad test. CONCLUSIONS: This temperature-sensitive device offers a new method for detecting urinary incontinence during LTAM studies. It can be fitted in an unobtrusive perineal pad and has a higher sensitivity and specificity for the detection of incontinence when compared to a pad test. It may also be used as a marker of voiding in ambulatory studies not employing an integrated voiding channel.
Female↗
Ras-Raf complexes: analyses of complexes formed in vivo.
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Animals↗
A cost-effective peripheral venous port system placed at the bedside.
High costs and a paucity of available operating time have led us to seek alternatives to operatively placed vascular access systems. This prospective study is the initial report of a peripheral port system (P.A.S. PORT System, Pharmacia Deltec, Inc.) placed at the bedside. Seventy-nine patients (52 male, 27 female), ages 3-92 years, had ports implanted by surgical residents with attending supervision. Sixty-eight (86%) received the P.A.S. PORT for long-term antibiotics, antifungal, or antiviral therapy; four (5%) for TPN infusion; three (4%) for blood products; two (3%) for chemotherapy; and two (3%) for iv narcotics. Ports were placed in 10 (13%) HIV(+) patients, three (4%) who were fully anticoagulated, and one who was a hemophiliac with a platelet count of zero. Eight patients (10%) developed superficial phlebitis, all of which resolved with nonsteroidal anti-inflammatory agents within 48 hr without port removal. Seven patients (9%) had their port removed due to infection. The average hospital charge to place the P.A.S. PORT System was $1488.00 vs $2811.00 for a tunneled external chest catheter and $3729.00 for the placement of a chest port. Bedside insertion of vascular access devices can be safely performed with acceptable infection rates allowing more efficient use of hospital operating rooms and with substantial cost savings.
Adolescent↗
The classwide peer tutoring program: implementation factors moderating students' achievement.
We conducted a study designed to assess implementation of the classwide peer tutoring program and the relationship between implementation variation and student outcome. A clinical replication design was used. Five volunteer elementary teachers were trained to implement the program; their implementation was monitored for 19 consecutive weeks during 1 school year. Overall, the results indicated that specific variations in program implementation were associated with students' responses to treatment. It was also demonstrated that different teachers' applications of the program produced differential levels of student outcome. Implementation factors related to lower spelling achievement were (a) reduced opportunities to receive program sessions, (b) reduced probabilities of students' participation in program opportunities, (c) too many students assigned unchallenging spelling words, and (d) reduced rates of daily point earning reflecting lower levels of spelling practice during tutoring sessions. The implications of these findings and methods of preventing these implementation problems are discussed in the context of quality assurance and social validity.
Achievement↗
Measurement of lithotripsy pulses through biological media.
Lithotripsy is now the method of choice for the treatment of renal calculi. The mechanism of destruction is not clearly understood, and detailed knowledge of the shock-wave characteristics at the calculus would aid understanding of the phenomenon. Current methods of measuring the pressure pulse by observing it through a water path are not well characterized, and the results may not represent the actual pressure fluctuations produced in vivo. In order to determine the actual pressure pulse experienced at the site of the calculus, measurements have been made through a variety of biological media. The results show that there are considerable differences between measurements taken through a water path and through biological media. This paper describes the pressure fluctuations in the time domain. The implications of the results for lithotripsy are discussed.
Animals↗
Improvement of platelet counts in steroid-unresponsive idiopathic immune thrombocytopenic purpura after short-course therapy with recombinant alpha 2b interferon.
In 13 patients with severe steroid-refractory idiopathic immune thrombocytopenia (ITP), a short course of recombinant alpha 2b interferon (IFN), given at a dose of 3 MU for 12 doses, caused a significant increase in platelet count in 11 patients. The rise in platelet count occurred following completion of the short course of IFN in 10 patients and occurred during therapy in one patient. Three patients showed an increase to normal platelet counts within 14 days of discontinuing the drug, eight showed a partial response, with a platelet count increase from 30 to 100 x 10(9)/L, and two patients showed minimal response. One complete responder relapsed at 5 months from initial response, and a further course of alpha 2b IFN caused a second prompt response with a rise of platelet count to supranormal levels. Short-course alpha 2b IFN can be recommended as a therapy for severe ITP. Responses are seen in splenectomized and nonsplenectomized subjects, and thrombocytopenia is not exacerbated during treatment.
Autoimmune Diseases↗
A comparative study of combination chemotherapy versus marrow transplant in first remission in adult acute lymphoblastic leukaemia.
The results of conventional chemotherapy in adult acute lymphoblastic leukaemia (ALL) have not improved substantially in recent years. The present study is based on a flexible policy of marrow transplantation (allograft and autograft without marrow purging) in first remission compared with a group treated with standard maintenance therapy after a common induction sequence. The actuarial disease free survival (DFS) and actuarial overall survival (OS) at 3 years for autologous marrow grafted patients was 30% and 65% respectively. The allogeneic transplant group had DFS of 30% and OS at 3 years of 38% compared with DFS (12%) and OS (12%) for patients on 6-mercaptopurine and methotrexate maintenance. The actuarial disease free survival calculations include patients on protocol not entering remission, therefore, giving the worst possible result. We conclude that high dose chemo/radiotherapy with autologous marrow rescue in first remission followed by no maintenance provides better results in terms of overall survival and quality of life than standard ALL maintenance in adult patients. Results for allogeneic transplant in ALL are less good in terms of duration and quality of survival and the majority of deaths are related to causes other than leukaemic relapse.
Adolescent↗
Splenic artery pseudoaneurysm after placement of percutaneous transgastric catheter for a pancreatic pseudocyst.
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Adult↗
Characterization of a timing mutant of Dictyostelium discoideum which exhibits "high frequency switching".
The preaggregative period of Dictyostelium discoideum is composed of two sequential rate-limiting components. The timing mutant FM-1 exhibits a decrease in the length of the preaggregative period and the interval between the maxifinger and early culminate II stage. In contrast, it is normal in all aspects of growth, in the sequence of morphogenetic stages, in spore formation, in the capacity to rapidly recapitulate morphogenesis, and in the erasure event and subsequent program of dedifferentiation. By the reciprocal shift experiment, it is demonstrated that FM-1 is completely missing the first of the two rate-limiting components comprising the preaggregative period. The FM-1 mutation is heritable and behaves as a single mutation mapping to linkage group II. However, the FM-1 variant switches at relatively high frequency to several other timing phenotypes with longer preaggregative periods which in turn switch at high frequency. The FM-1 phenotype is considered in terms of timing regulation, and the process of high frequency switching between timing phenotypes is compared to other newly discovered switching systems.
Animals↗
Gene regulation during dedifferentiation in Dictyostelium discoideum.
During development of Dictyostelium discoideum, cells acquire the capacity to rapidly recapitulate morphogenesis. Therefore, when cells at the loose aggregate stage are disaggregated and challenged to reaggregate, they do so in a tenth of the original time. If loose aggregate cells are disaggregated and resuspended in buffered dextrose solution (erasure medium), they retain the capacity of rapid recapitulation for 80 min, then completely lose this capacity in a single, synchronous step referred to as the "erasure event." The erasure event sets in motion a program of dedifferentiation during which cells lose developmentally acquired characteristics at different times. The erasure event is inhibited by the addition of 10(-4) M cAMP to erasure medium. The synthesis of 33 growth-associated polypeptides, the synthesis of 53 development-associated polypeptides, and the level of 2 development-associated RNAs have been monitored during the erasure program and in cultures inhibited from erasing by the addition of 10(-4) M cAMP. Growth-associated polypeptides begin to be resynthesized and development-associated polypeptides exhibit dramatic decreases in rate of synthesis at different times throughout the first 240 min in erasure medium. Inhibiting the erasure event with cAMP has no major effect in the resynthesis of the majority of growth-associated polypeptides. Only one growth-associated polypeptide, V28, is completely inhibited by cAMP, suggesting that it may play a role in the erasure process. In contrast, inhibiting the erasure event with cAMP has a marked effect on the synthesis of development-associated polypeptides, causing a dramatic reduction in the rate at which synthesis decreases for 6 polypeptides, and completely inhibits the decrease in the synthetic rate of 8 polypeptides. The two development-associated RNAs, 16G1 and 10C3, exhibit two distinctly different patterns of loss during erasure, but in both cases cAMP added at time zero of the erasure process dramatically retards or inhibits loss. In addition, when cAMP is added just prior to the erasure event, it inhibits the erasure event and stimulates a rapid increase in the level of 16G1 RNA back to the developmental level. The level of 16G1 RNA then remains at this level for at least 400 min. When cAMP is added after the erasure event, it causes a low, transient increase in the level of 16G1 RNA. These results are considered both in relation to the program of erasure, and in relation to the role of cAMP in the expression of developmental genes during the forward program of development.
Cell Differentiation↗
Intraperitoneal administration of an I125 labelled monoclonal antibody for localization of human colorectal cancer in the nude mouse.
The monoclonal antibody (MoAb) HMGF-1 was evaluated in the radioimmunodetection of human colonic cancer transplanted intraperitoneally (i.p.) into athymic nude mice. This antibody reacts with a component of the human milkfat globule, as well as a wide range of epithelial cells and adenocarcinomas of various origins. Purified MoAb was iodinated with 125I and administered i.p. into nu/nu mice bearing (i.p.) xenografts of human colonic adenocarcinoma (X56). Differential tissue counts of radioactivity demonstrated preferential localization of the antibody in i.p. and subcutaneous (s.c.) tumor tissue as compared to normal tissues. Maximum per cent dose per g of tumor (25.17 +/- 1.37), maximum tumor: blood ratio (4.45 +/- 0.14) and maximum tumor: tissue ratios (34.2 +/- 0.12) were obtained at the optimal labelling time of 5 days after antibody injection. Selective localization to tumor was confirmed with a control anti-hepatitis virus MoAb of the same isotype and by localization studies in non-tumor bearing athymic mice. Half lives of the persistence of the iodine 125 in the tumor bearing and non tumor bearing mice were 5 and 7 days, respectively, indicating approximate antibody half lives. Whole body scans showed distinct tumor images without the use of subtraction techniques. This pilot experimental study demonstrates the feasibility of i.p. administration of labelled antitumor MoAb in the imaging of i.p. tumors in an athymic mouse system. Whether or not these observations are applicable to the human situation remains to be carefully established.
Adenocarcinoma, Mucinous↗
Observations on dermal blood flow as reflected by technetium-99m pertechnetate clearance.
Skin blood flow as reflected by the clearance rate of intradermal injections of Technetium-99m (99mTc) was studied in the skin of human volunteers and in a variety of clinical situations. In volunteers comparisons between the effect on clearance following intradermal injections of either lignocaine or lignocaine/adrenaline showed that the latter resulted in a dramatic reduction in the clearance rate of the technetium isotope and that such clearance curves exhibited no fast component. Clinical studies in grossly ischaemic skin revealed a similar absence of the fast component of isotope clearance and this was also the case for healed split thickness skin grafts. The dermal isotope clearance was also used in pedicle skin flaps both before and after clamping the axial pedicle in order to derive clearance ratios which would reflect the degree of neovascularisation to the flap. These preliminary observations suggest that the technique is safe, and easy to use in many clinical circumstances. We consider that it offers a valuable method by which changes in dermal blood flow may be quantified, when simultaneous control areas of isotope clearance are also studied. Suggestions are made for further avenues of study.
Adult↗
The programs of protein synthesis accompanying the establishment of alternative phenotypes in Candida albicans.
Under the regime of pH-regulated dimorphism, stationary phase cells of the dimorphic yeast Candida albicans can be induced to form exclusively and synchronously ellipsoidal buds or elongate mycelia at the same temperature and in the same nutrient medium, the sole determinant of phenotype in this case being pH. Employing pH-regulated dimorphism, cells were pulse-labeled with [35S]-methionine during three consecutive intervals encompassing the preevagination period, the period including evagination and phenotypic commitment, and the post-evagination period. Labeled polypeptides were analyzed by 2D-PAGE. Of the 374 polypeptides examined, the majority (237) did not differ significantly in relative incorporation between the three pulse periods and were similar between budding and mycelium-forming populations. Sixty polypeptides were labeled at negligible or relatively low levels during the first pulse period, but at significantly higher levels during the second and third or third pulse periods. All but one were similar between budding and mycelium-forming populations. Seventeen polypeptides were synthesized at relatively high levels during the first pulse period, but at reduced or negligible levels during the second and third or third pulse periods. All but one were similar between budding and mycelium-forming populations. Only two polypeptides were found to be associated exclusively with mycelium-forming cultures, two associated exclusively with budding cultures, and two enriched significantly in budding cultures of wild-type cells. Employing a variant, MD20, which forms buds at both low and high pH, it was demonstrated that only one mycelium-associated polypeptide and only one bud-associated polypeptide are phenotype rather than pH-specific. Limits to this method of phenotype comparison are outlined, and the unusual similarity rather than dissimilarity in the programs of gene expression between the diverging populations considered in terms of phenotypic regulation.
Candida albicans↗
Acute lymphoblastic leukaemia in adults in the northern region of England--a study of 75 cases.
Over a ten-year period we have studied 75 cases of adult acute lymphoblastic leukaemia (ALL). Sixty of the cases were seen from 1979 to 1984 and represent an unselected series of all known cases in a region of 3 000 000 people. Study of these patients has given further insight into the heterogeneous, clinical and cytological nature of adult ALL. Three protocols have been used and results are presented indicating that conventional approaches to treatment in this disease are unsatisfactory. Not all patients could be entered on protocols but these patients are included to give the overall perspective of this disease in clinical practice. A new strategy is proposed which envisages abandoning traditional maintenance chemotherapy in favour of either allogeneic marrow transplant or autologous transplant in first remission in the post-consolidation phase. Preliminary results of this flexible approach are given.
Acute Disease↗