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The location of the Philadelphia chromosomal breakpoint site and prognosis in chronic granulocytic leukemia.

Chronic granulocytic leukemia (CGL) is associated with a reciprocal translocation between chromosomes 9 and 22. The breakpoint sites on chromosome 22 are clustered in a limited region known as the major breakpoint cluster region (Mbcr). This region is approximately 5.8 Kb long and can be arbitrarily subdivided into five zones (1 through 5 from the 5' towards the 3' end) as defined by the particular sites of three restriction endonucleases. Using Southern blot analysis with two DNA probes, one spanning both the 5' and 3' regions of the Mbcr while the other only the 3' region, we mapped the precise location of the chromosomal breakpoints within the Mbcr in 62 patients with CGL and examined possible clinical correlations. There were 39 patients with 5' breakpoints (zones 1-3) and 23 patients with 3' breakpoints (zones 4 and 5). We found no correlation between the clinical phase of the disease at last followup and breakpoint distributions. The distributions of chronic phase duration (CPD) and survival were similar between patients with 5' breakpoints (median CPD = 4.0 years) and those with 3' breakpoints (median CPD = 5.2 years). Presenting clinical features and the rates of lymphoblastic transformation were also similar among the subgroups. Our data suggest that the precise location of the breakpoint within the Mbcr in CGL may not have clinical relevance.

Blast Crisis↗

Effect of storage on oxygen dissociation of canine blood.

Oxygen dissociation curve and adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (DPG) contents in red blood cells (RBC) were determined in canine blood stored in acid citrate dextrose (ACD) and citrate phosphate dextrose (CPD) solutions. The oxygen-unloading ability decreased, as shown by the left shift of oxygen dissociation curve during storage, and the shift correlated with decreasing DPG but not decreasing ATP concentrations. After 2 weeks of storage in ACD solution, oxygen dissociation curves were shifted significantly to the left. For blood stored in CPD solution, 4 weeks was required before the shift was significant. It was concluded that canine blood collected and stored in CPD solution is more efficient than that stored in ACD solution in delivering oxygen to the tissues.

Adenosine Triphosphate↗

[Pulmonary arterial input impedance in patients with chronic pulmonary diseases].

To evaluate pulmonary vascular lesions, input impedance of pulmonary arterial system was determined in 52 patients with chronic pulmonary diseases (CPD) by using a multisensor catheter. Mean values of impedance parameters in 14 subjects with normal mean arterial pressure (less than 15 mmHg) were 31 +/- 3 dyne.sec.cm-5 in characteristic impedence (Zo), 3.5 +/- 0.3 Hz in the frequency at which the first minimum of the impedance modulus occurs (fmin) and 0.85 +/- 0.3 in Zx oscillation (Zxos). In patients with CPD, Zo increased with an elevation of pulmonary arterial pressure (p less than 0.01) and fmin shifted to the right with that (p less than 0.05). These results show that stiffness of the proximal arteries in CPD is increased. In patients of interstitial fibrosis with pulmonary arterial hypertension, Zo was not significantly increased, but fmin shifted to the right. Pulse wave velocity correlated with fmin, but did not correlate with Zo. In conclusion, these results suggest that analysis of pulmonary arterial input impedance with a multisensor catheter provides useful information for patients with pulmonary hypertension.

Aged↗

[Continuous peritoneal dialysis in children].

Thirty-two uremic children were treated by chronic peritoneal dialysis (CPD) since February 1982. Fifteen chose chronic ambulatory peritoneal dialysis (CCPD) while the 17 others were treated by continuous cycle peritoneal dialysis (CCPD). To this day, 10 patients (31%) are alive with a functioning kidney transplant, 16 (50%) are still treated by CPD awaiting a transplant, 5 have died (16%) and one went back to hemodialysis (3%). Complication in ranking order were peritonitis, mechanical drainage problems of the catheter and hernias. Linear growth was from good to excellent in the majority of patients. Globally, CPD was found to be attractive mainly because it allows a good quality of life.

Adolescent↗

Disparity range for binocular summation.

Binocular summation of contrast and stereopsis have been linked because they both disappear under certain pathological conditions. The dependence of stereopsis on spatial frequency prompted us to examine how binocular summation varies with both spatial frequency and binocular disparity. We therefore measured binocular summation at different disparities using spatially localized stimuli which were also restricted in their Fourier composition. Contrast thresholds were measured using three interleaved forced-choice staircases for left and right eye monocular stimuli and a binocular stimulus composed of the two monocular stimuli presented simultaneously. At zero disparity binocular thresholds were 1.4 to 1.6 times lower than monocular. As disparity was increased the ratio between the thresholds became smaller, such that at large disparities it was near 1.2, the value expected from probability summation. The range of disparities over which probability summation was exceeded varied with the spatial frequency of the stimulus. At 6.0 cpd the range was 2-3 deg, but at 2.0 cpd or 0.75 cpd the range increased to 4-6 deg. These values closely parallel the range of disparities over which stereoscopic depth sensations occur, but they exceed the limits within which disparate images of an object can be fused into a single percept. The results support the contentions that "neural" summation occurs in the mechanism for stereopsis, that this mechanism uses spatial frequency selective channels, and that this mechanism is separate from the mechanism which mediates fusion.

Adult↗

[The influence of the right or left ventricular pressure overload on right and left ventricular diastolic behaviors as examined by pulsed Doppler echocardiography].

The influence of morphological and dynamic changes in the interventricular septum (IVS) on right ventricular (RV) and left ventricular (LV) fillings in cases of LV or RV pressure overload was evaluated. Using pulsed Doppler echocardiography, LV and RV inflow signals were recorded in 20 healthy subjects, in 36 cases of chronic pulmonary disease (CPD) with pulmonary hypertension, and in 46 cases of essential hypertension (HT). Two-dimensional short-axis echocardiograms were recorded at end-diastole (ED) and end-systole (ES) in the healthy subjects and in the cases with CPD. M-mode echocardiograms of the LV were recorded in the healthy subjects and in the cases with HT. We measured (1) the ratio of the peak velocity of inflow due to atrial contraction to that of rapid inflow (A/R), (2) the deceleration half-time of rapid inflow (delta TD), (3) the corrected radius of curvature of the IVS at ED and ES, (4) the % change of lengthening (CL) of 16 radial grids using a fixed method on the ED and ES short-axis images, and (5) the IVS end-diastolic thickness (IVSEDTh). The results were as follows: 1. In the patients with CPD, (1) the diastolic behavior was impaired not only in the RV, but in the LV as well, as shown by the increased A/R and prolonged delta TD in both ventricles, (2) the IVS was flattened at ED, as shown by the decreased corrected radius of the curvature, (3) the regional wall motion of the IVS was impaired, as shown by the decreased CL of the IVS. 2. In the patients with HT, (4) the RV diastolic filling was not impaired, (5) the LV A/R correlated with IVSEDTh, but the RV A/R did not correlate with IVSEDTh. We concluded that RV pressure overload interferes with IVS motion during diastole, and that the regional impairment of diastolic behavior of the IVS causes impairment of LV diastolic filling. Furthermore, the increased IVS wall thickness due to LV pressure overload has a little or no influence on the RV inflow pattern because the RV free wall was so distensible as to overcome the effect of increased IVS stiffness.

Aged↗

Tissue responses of the monkey retina: tuning and dependence on inner layer integrity.

Recent technical and conceptual advances have made it possible to experiment with models of local human inner retinal disease and changes in very small, tissue-specific signals. Local retrograde degeneration of the ganglion cells was induced in four rhesus monkeys by 160 degrees microdiathermy fiber layer burns at the nasal or temporal edges of the optic disc. There were no abnormalities of the classical electroretinograms (ERGs) during the following 210 days. With nasal lesions, pattern-evoked retinal (PERR) and cortical responses over a range of grating contrasts and spatial frequencies were largely normal. The authors found a cortical spatial tuning peak near 0.5 cycles/deg (cpd) and a retinal peak at 0.25-0.3 cpd. With temporal lesions, the retinal signals to high frequency stimuli (greater than 1.0 cpd) approached zero between 20-60 days. The cortical evoked signal declined with a course similar to the retinal components. Histological evidence was found for extensive loss of ganglion cells and fibers in a central 30-40 degrees temporal area, including the macula, 210 days after the temporal lesions. This is strong evidence that local ganglion cell-dependent electrical potentials, bearing little relation to the ERG, can be measured in response to selected stimuli.

Animals↗

Microinjection study of renal calcium absorption in the phosphate-depleted rat.

Tracer microinjection studies were performed in chronically phosphate-depleted (CPD) and phosphate-supplemented (PS) rats in order to determine the site of the defect in calcium absorption which developed in CPD. Calcium recovery in the final urine was significantly higher in CPD than in PS rats after microinjections into the early and the late proximal tubules. However, there was no significant difference in the urinary recovery between the two groups after injection into the early and late distal convoluted tubules. The difference in calcium recovery in late proximal studies persisted during PTH infusion. This indicates that there is a defect in calcium absorption in phosphate-depleted rats between late proximal and early distal tubules, which is not correctable with PTH infusion.

Animals↗

Preservation of red blood cells with purines and nucleosides. II. Uptake and utilization of purines and nucleosides by stored red blood cells.

The uptake of adenine, guanine, guanosine and inosine by stored red cells was investigated in whole blood and red cell resuspensions at initial concentrations of 0.25, 0.5 and 0.75 mM for adenine and 0.5 mM for the other additives using a rapid ion-exchange chromatographic microanalysis of purines and nucleosides in plasma and whole blood. Increasing adenine concentrations from 0.25 to 0.75 mM in blood elevated the adenine uptake from 0.3 up to 0.8 mmol/l red cells during 2 hours after collecting blood. The intra-/extracellular distribution ratio changed from 1 : 1.3 to 1: 1.7. Some 2 hours after withdrawing blood into CPD--solution with purines and nucleosides the uptake of adenine and guanine resulted in 40 per cent and 70 per cent respectively and of guanosine and inosine in 80 and 90 per cent respectively. The replacement of plasma by a resuspending solution gave the same uptake rates for purines and nucleosides. The nucleosides were rapidly split to purines and R-1-P and disappeared from blood during one week. Adenine and guanine were utilized to 80 to 90 per cent only after 3 weeks. During the same period the utilization of guanine was smaller by 40 per cent than that of adenine due to the different activity of the purine nucleoside phosphorylase for these substrates. The plasma of all analyzed blood samples contained hypoxanthine and inosine, but guanine and guanosine were detected only in those samples to which one of them was added. After 3 weeks of storage the highest concentration of hypoxanthine was found in CPD-AI blood with 600 microM in plasma and the highest concentration of synthesized inosine in CPD-AG blood with a concentration of 100 microM in plasma. Three ways of utilization of purines by stored red cells were discussed : the synthesis of nucleotide monophosphates, the formation of nucleosides, and the deamination. The portions of these ways change during storage. The most effective concentrations of adenine and guanosine in stored blood seems to be 0.25 and 0.5 mM respectively. The full utilization of the nucleoside requires the addition of inorganic phosphate.

Adenine↗

Storage requirements for erythrocytes used to culture Plasmodium falciparum.

Erythrocytes stored for up to 84 days in citrate-phosphate-dextrose (CPD), CPD-adenine, saline-glucose, saline-glucose-adenine, or as packed cells were tested after varying lengths of time for suitability to support cultures of Plasmodium falciparum using the Petri dish-candle jar technique. All storage protocols were adequate for 21 to 28 days with those media containing adenine being generally better and packed cells poorer than CPD. Erythrocyte ATP contents generally correlated well with the suitability of stored erythrocytes for supporting falciparum parasite cultures. However, rejuvenation procedures, which markedly elevated ATP concentrations in erythrocytes, resulted in erythrocytes less suitable for parasite development. Erythrocytes stored between 4 to 12 days were usually somewhat less suitable than freshly collected, or after 12-plus days of storage. The presence of leucocytes undergoing disintegration during the first week of storage had no measurable effect on the suitability of the erythrocytes because both leucocyte-rich and leucocyte-poor blood portions supported parasite development equally. Likewise, leucocytes present with parasites in the cultures, had no measurable effect on parasite development.

Adenine↗

A phase-specific adaptation effect of the square-wave grating.

The existence of wide-band, phase-specific channels in the human visual system has been suggested in recent investigations. We used a number of adapting gratings to test for phase-specific adaptation effects. Observers were asked to discriminate between a simple 3 cpd sine-wave grating, (3), and a complex grating composed of this (3) plus a 9 cpd grating combined in one of two phases: peaks-subtract, (3,9:0), or peaks-add, (3,9:pi). The results show a significant phase-specific adaptation effect. That is, following adaptation to a square-wave grating, discrimination performance for (3,9:0) vs. (3) deteriorated significantly more than for (3,9:pi) vs. (3). Adaptation to the first two harmonics of the square-wave, (3,9:0), or a 3 cpd triangle-wave grating failed to produce phase-specific adaptation effects that reached significance.

Adaptation, Ocular↗

[Mechanical intraoperative autotransfusion].

The cardiac effects during maximum pressure autotransfusion of blood which was anticoagulated by different methods, were studied in 2 series of 9 dogs. The animals, which were anaesthetized and splenectomized, received each 300 i.v. heparin/kg bodyweight intravenously before being subjected to repeated maximum pressure auto-transfusions of 10% of their whole blood volume. The anticoagulant employed during each autotransfusion was changed in station as follows: Heparin-(ACD-B)-Citrate-Heparin-CPD-Citrate... and so on. Criteria of cardiac efficiency, signs of insufficiency, pumpfunction (force of contraction, contractility) were all derived from the 4 phases of the aortic pressure tracing. In addition various parameters of the ECG, using the "Colletti distances", were measured. The results were proved by laboratory data. Immediately after the pre-determined bleeding (V) there was a characteristic fall of all parameters corresponding to the acute reduction in circulating blood volume, which returned to normal after the autotransfusion was completed (G). During the transitory phase S all data remained stable when heparin had been employed as the anticoagulant. Following the use of citrate, however, particularly CPD, there was an ensuing fall in all accounted for by the acute withdrawal of Ca++ which could be measured. Subsequently the circulation stabilized (ST) spontaneously and all parameters being measured returned to their original values when heparin and ACD-B had been used. With CPD, however, the force of contraction, enddiastolic pressures and propagation of electric activity of the heart were still altered.

Animals↗

X-ray pelvimetry: helpful or harmful?

This study was performed (1) to clarify the usefulness of x-ray pelvimetry in diagnosing cephalopelvic disproportion (CPD), particularly in patients with abnormal labor, and (2) to examine the association between infant birthweight and mode of delivery. The subjects were 100 consecutive patients who underwent x-ray pelvimetry. A retrospective chart review was done to collect demographic data and evaluate Friedman labor curves. Radiologic dimensions were tabulated for anteroposterior diameter, transverse diameter, and summation plane values of both inlet and midpelvic planes. Average pelvimetric values for subjects delivered vaginally and those delivered abdominally were compared, and Hotelling's T2 analyses were conducted to determine whether the differences were statistically significant. Average birthweights of infants born to women in cesarean section and vaginal delivery groups were also compared, with t tests conducted to determine statistical significance. Results showed that even in a select group of patients in abnormal labor with the highest probability of CPD--a condition it was believed x-ray pelvimetry could diagnose--no significant difference in bony pelvic dimensions existed between vaginal and cesarean delivered patients. The cesarean group did, however, deliver significantly heavier infants. The results question the usefulness of x-ray pelvimetry in diagnosing CPD.

Birth Weight↗

Further studies of specimen volume changes during processing for SEM: including some plant tissue.

The dimensions of specimens undergoing preparation for examination in the SEM were measured throughout the preparative sequence or at various important stages. The tissues studied included 15-day mouse embryo limbs (MEL), small blocks of adult mouse liver and brain, and potato tuber. The animal tissues were fixed in 3% glutaraldehyde (GA) in 0.15M cacodylate buffer, and the potatoe tissue in 2% GA in water. The effects of various secondary fixation and other treatments were investigated. The results show that lithium salts cause a reduction in the shrinkage of MEL in 100% ethanol but this effect was not significant in the other tissues investigated, and did not persist in specimens stored after critical point drying (CPD). All CPD specimens were shrunken. However postosmication and treatment with uranyl acetate (UAc) and cetyl pyridinium chloride (CPC) all reduced specimen shrinkage in 100% ethanol and after critical point drying. The volume gains with Os + UAc and Os + CPC are both very significant, but it was found that these larger specimens shrank more on storage. Thus rapid examination in the SEM is recommended. Ethanol and Freon 113 were compared as intermediate fluids and it was found that ethanol-CO2 critical point dried specimens shrank more before and after CPD than Freon 113-CO2 specimens. The latter technique is, therefore, to be recommended. Potato tissue shrinks in 30% ethanol, whereas animal tissues all swell in this concentration. The potato tissue also shrank very litte on critical point drying in contrast to the animal tissue specimens.

Animals↗

Increased calcium permeability of cold-stored erythrocytes.

The calcium, sodium, and magnesium permeability of erythrocytes from blood stored at 4 degrees C in various anticoagulant media has been studied and compared to that of fresh erythrocytes. Passive influx of CA2+ was measured at 37 degrees C in cells pretreated to abolish Ca2+ pumping and was up to fivefold greater for cold-stored erythrocytes than for fresh cells. The Ca2+ leakiness developed gradually after day 2 and reached a maximum by day 7 of cold storage in ACD, CPD, CPD-adenine, or heparin anticoagulants. The total calcium content of cold-stored erythrocytes in ACD was not significantly different from that of fresh erythrocytes. However, when cold-stored erythrocytes were reincubated at 37 degrees C in media containing 1.5 mM ionized calcium and substrates to regenerate ATP, a net gain of Ca2+ occurred that was greater for stored than for fresh erythrocytes. Cold storage of blood for up to 6 wk in any anticoagulant did not alter either sodium or magnesium permeability. Red cell ATP was also measured and fell steadily during cold storage in ACD or CPD, but more increase in Ca2+ permeability preceded any significant change in red cell ATP, it is likely that a selective calcium leak develops independently of the fall in ATP concentration that occurs on cold storage.

Adenosine Triphosphate↗

Red blood cell preservation in protein-poor media. 2. Studies of changes in red cell shape during storage.

Red cells stored for up to 35 days have been studied by scanning electron microscopy. Formation of spicules occurred under all storage conditions in CPD and CPD-adenine whole blood, CPD-adenine red cell concentrate, and saline-adenine-glucose red cell concentrate. The number of cells with normal or near normal shape was larger if the blood was stored as a moderately concentrated suspension in saline-adenine-glucose medium or in autologous plasma as compared to the storage as whole blood. The occurrence of echinocytes during storage at +4 degrees C was not correlated to red cell ATP. It was shown that a drastic reduction of ATP leads to an increased formation of both spherocytes and echinocytes. The change of red cell shape during storage at +4 degrees C thus can be due to two processes, one unrelated to ATP and another related to ATP. Why storage as red cell concentrate is superior is not fully understood.

Blood Specimen Collection↗

Different removal of ultraviolet photoproducts in genetically related xeroderma pigmentosum and trichothiodystrophy diseases.

To understand the heterogeneity in genetic predisposition to skin cancer in different nucleotide excision repair-deficient human syndromes, we studied repair of cyclobutane pyrimidine dimers (CPDs) and of pyrimidine(6-4)pyrimidone (6-4PP) photoproducts in cells from trichothiodystrophy (TTD) patients. TTD is not associated with increased incidence of skin cancer, although 50% of the patients are photosensitive and carry a defect in the nucleotide excision repair pathway, similar to Xeroderma pigmentosum patients. However, in striking contrast to TTD, Xeroderma pigmentosum is highly prone to cancer. To address this apparent paradox, two types of studies were conducted: (a) reactivation of UV-irradiated plasmids harboring actively transcribed reporter genes, with or without photolyase treatment before transfection of SV40-transformed fibroblasts; and (b) the kinetics of removal of UV-induced CPDs and 6-4PPs in genomic DNA by immunoblot analysis using lesion-specific mAbs in SV40-transformed and untransformed fibroblasts representative of all genetic TTD complementation groups. Results showed that all cell lines from photosensitive TTD patients efficiently express Cat or luciferase genes in transfected plasmids carrying non-CPD lesions, including 6-4PP, and display wild-type or near-wild-type (50-70% in 3 cell lines) 6-4PP repair in the overall genome after immunoblot analysis. However, CPD lesions (the repair of which is defective in the overall genome) also block the expression of the reporter gene in transfected plasmids. Two cell lines from nonphotosensitive TTD patients showed wild-type levels of repair for both photoproducts in overall genome. A model on the lesion-specific repair in the context of the molecular defect in TTD is proposed. The implication of the defective CPD repair and efficient 6-4PP repair subpathways in cancer prevention in TTD patients is discussed.

Cell Line↗

Influence of a corpus luteum tissue extract on rabbit ovarian mesothelial cells.

This study investigates rabbit ovarian mesothelial (OM) cells exposed in vitro to a crude corpus luteum extract (CLE; 60 micrograms/ml). The growth of OM cells was evaluated by measuring the change in cell number (mean % +/- standard error of mean, SEM), the number of cell population doublings (CPD +/- SEM), and the cell population doubling time in hours (CPDT +/- SEM) after 7.5 days of culture in a serum-poor medium. Quantitative estimates of surface morphology changes were obtained by analyzing the total number (mean no. +/- SEM), density (mean no./100 microns 2 +/- SEM), and length-to-diameter ratio (mean L/D +/- SEM) of microvilli. OM cells in control medium formed loosely cohesive monolayers, and grew 152.53 +/- 11.01% with a CPD of 0.59 +/- 0.08 and a CPDT of 117.29 +/- 6.43 hours. The exposed surface area of these cells was over 8,000 microns 2 and was covered in its epinuclear region by long and slender microvilli with a L/D of 6.01 +/- 0.29. The total number of microvilli in each control cell was 1977.52 +/- 120.49 with a density of 0.58 +/- 0.03/100 microns 2 in the epinuclear region and of 0.05 +/- 0.003/150 microns 2 in the remaining surface area (5,161.62 +/- 354.43 microns 2). In contrast, CLE-rich cells cultures grew 329.57 +/- 16.65%, with a CPD of 1.71 +/- 0.07 and a CPDT of 53.43 +/- 2.93 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗