First Evidence of Axial Shape Asymmetry and Configuration Coexistence in

The excited states of N=44 ^{74}Zn were investigated via γ-ray spectroscopy following ^{74}Cu ß decay. By exploiting γ-γ angular correlation analysis, the 2_{2}^{+}, 3_{1}^{+}, 0_{2}^{+}, and 2_{3}^{+} states in ^{74}Zn were firmly established. The γ-ray branching and E2/M1 mixing ratios for transitions deexciting the 2_{2}^{+}, 3_{1}^{+}, and 2_{3}^{+} states were measured, allowing for the extraction of relative B(E2) values. In particular, the 2_{3}^{+}→0_{2}^{+} and 2_{3}^{+}→4_{1}^{+} transitions were observed for the first time. The results show excellent agreement with new microscopic large-scale shell-model calculations, and are discussed in terms of underlying shapes, as well as the role of neutron excitations across the N=40 gap. Enhanced axial shape asymmetry (triaxiality) is suggested to characterize ^{74}Zn in its ground state. Furthermore, an excited K=0 band with a significantly larger softness in its shape is identified. A shore of the N=40 "island of inversion" appears to manifest above Z=26, previously thought as its northern limit in the chart of the nuclides.

Long-Term Mean Vertical Motion over the Tropical Pacific: Wind-Profiling Doppler Radar Measurements.

Measurement from Christmas Island (2 degrees N, 157 degrees W) of long-term mean vertical motions in the tropical atmosphere using very-high-frequency wind-profiling Doppler radar show that there is a transition from downward motion in the free troposphere to upward motion in the upper troposphere and lower stratosphere. The observations in the free troposphere are consistent with a balance between adiabatic and diabatic heating and cooling rates in a clear atmosphere. Comparison of the results at Christmas Island during El Niño and non-El Niño conditions with earlier results obtained for stratiform rain conditions over Pohnpei, Federated States of Micronesia, show that cirrus clouds in the vicinity of the tropopause likely play an important role in determining the sense and magnitude of vertical motions in this region. These results have implications for the exchange of mass between the troposphere and stratosphere over the tropics.

Biodistribution of 125I-labeled des(1-3) insulin-like growth factor I in tumor-bearing nude mice and its in vitro catabolism.

Insulin-like growth factor I (IGF-I) is a potent mitogen for many tumor cell lines, and IGF-I receptors are overexpressed in many tumors. Specific IGF-binding proteins (IGFBPs) modulate the interaction of IGF and its receptors. Consequently, radiolabeled IGF-I has been considered for tumor imaging. In the present study, we investigated the biodistribution of 125I-labeled des(1-3)IGF-I, a truncated analogue of IGF-I, in tumor-bearing nude mice. Additional studies included its catabolism by tumor cells in vitro and its binding to serum IGFBPs in vivo in nude mice. We also compared groups that were and were not injected with unlabeled peptide analogue. Our data showed that 125I-labeled des(1-3)IGF-I catabolized very fast, with a rapid appearance of nonprecipitable iodine, when incubated at 37 degrees C, but it was not catabolized at 4 degrees C incubation. 125I-labeled des(1-3)IGF-I was bound to serum-binding proteins, mainly in a complex with a molecular weight of M(r) 150,000. The uptake of radioactivity in normal tissues decreased quickly with time, particularly in the kidneys. In mice receiving higher doses of des(1-3)IGF-I, the radioactivity in all normal tissues was lower than in the mice with no carrier-added des(1-3)IGF-I, except in the stomach and spleen. These data suggest that 125I-labeled des(1-3)IGF-I is rapidly internalized after binding to the IGF receptor and is rapidly catabolized with release of breakdown products. Lower specific activity of 125I-labeled des(1-3)IGF-I resulted in altered biodistribution, including faster blood clearance and higher tumor uptake, by decreasing the formation of complexes with IGFBPs.

The bZIP-like motif of hnRNP C directs the nuclear accumulation of pre-mRNA and lethality in yeast.

The hnRNP C protein tetramer cooperatively binds 230 nt increments of pre-mRNA in vitro in a salt-resistant manner and is located along the length of vertebrate transcripts in vivo. Based on these and other findings it has been suggested that hnRNP C functions as a chaperonin to maintain long lengths of RNA topologically single-stranded and accessible to splicing factors. We report here that human C protein is lethal when expressed in the yeast Saccharomyces cerevisiae. Through a series of fluorescent immunolocalization studies, lethality was observed to be associated with the rapid nuclear accumulation of both C protein and yeast pre-mRNA. Studies using various protein constructs and the two hybrid assay reveal that these events are dependent on the basic 40 residue high-affinity RNA binding domain and its contiguous leucine zipper-like motif (the bZLM, residues 140-214). Additionally, equilibrium binding studies have shown that the bZLM is the determinant of C protein's salt-resistant RNA binding mode. Taken together, these findings further distinguish the bZIP-like domain as the major determinant of C protein's high-affinity interaction with RNA, oligomerization, and its highly cooperative RNA binding activity. Finally, these findings indicate that yeast and vertebrates may possess a conserved mechanism for general import of RNP although a true homolog to vertebrate C protein appears not to exist in yeast. Lethality is likely due to the absence in yeast of specific mechanisms for the removal of human C protein from nascent transcripts.

Usefulness of physical examination in detecting the presence or absence of anemia.

Previous studies addressing the usefulness of pallor in anemia are deficient because of observer or spectrum bias. Three internists made individual assessments of conjunctivae, face, nails, palms, and palmar creases in 98 male and 5 female hospitalized patients at a Veterans Administration Medical Center. The true-positive rates (sensitivities) were highest for pallor at any one of three sites (ie, the conjunctivae, face, or palms; 0.65) and for pallor of the palms (0.53). True-negative rates (specificities) were best for palmar creases (1.00), for pallor at conjunctivae, face, and palms (all three in combination; 0.95), and for the face (0.90). Receiver operator characteristic curve analysis revealed that the examination of the nailbeds is inferior to all other sites or combinations. Interobserver variability K scores were negative for palmar creases but ranged from .16 to .51 for other sites. We conclude that (1) the absence of pallor does not rule out anemia, and therefore this sign is not useful for screening an asymptomatic population; (2) pallor of the conjunctivae, face, and palms together is of benefit in confirming the presence of anemia; and (3) neither the nailbeds nor palmar creases are of value in assessing the presence or absence of anemia.

Septic and nonseptic olecranon bursitis. Utility of the surface temperature probe in the early differentiation of septic and nonseptic cases.

Forty-six consecutive cases of olecranon bursitis were prospectively analyzed during a 1-year period. Eleven cases were septic; 35 cases were nonseptic. In addition to bursal fluid analysis, the surface temperature over the involved olecranon bursa and the contralateral (control) olecranon process was obtained by using a surface temperature probe. We compared the temperature difference between the involved and control sides in all septic and nonseptic cases. In nonseptic cases, the mean surface temperature difference was 0.7 degree C vs 3.7 degrees C in septic cases. In all septic cases, the temperature difference was 2.2 degrees C or greater (range, 2.2 degrees C to 5.1 degrees C; SD, 1.1). Use of the surface probe temperature difference proved 100% sensitive and 94% specific in discriminating septic from nonseptic cases. It seems to be more helpful than the bursal fluid leukocyte count, the predominant cell type, or Gram's stain in the early differentiation of septic and nonseptic olecranon bursitis.

Treatment of nonseptic olecranon bursitis. A controlled, blinded prospective trial.

We enrolled 42 patients with nonseptic olecranon bursitis in a double-blind prospective treatment trial to compare the efficacy of an intrabursal steroid preparation with that of an oral anti-inflammatory agent. Patients were randomized into one of four treatment regimens: (1) methylprednisolone acetate (20 mg) intrabursal injection and oral naproxen (1 g/d for 10 days), (2) methylprednisolone acetate (20 mg) intrabursal injection and oral placebo for 10 days, (3) oral naproxen (1 g/d for 10 days), and (4) oral placebo for 10 days. The degree of swelling in millimeters was assessed at study introduction and at 1, 3, and 6 weeks. At 6 months, the number of patients requiring reaspiration for bursitis recurrence was tabulated. Data at 1 week indicated that patients treated with an intrabursal methylprednisolone acetate injection (20 mg) demonstrated the most rapid decrease in swelling. At 6 weeks, the methylprednisolone-treated groups demonstrated sustained improvement. At 6 months, the mean number of reaspirations per patient for reaccumulation of bursal fluid was higher in groups 3 (1.0 +/- 1.2) and 4 (0.4 +/- 0.7). An intrabursal methylprednisolone acetate 20-mg injection seems to be the most effective treatment regimen for nonseptic olecranon bursitis.

Furosemide augments the effects of captopril on nuclear studies in renovascular stenosis.

Captopril facilitates detection of unilateral renovascular hypertension by selectively reducing glomerular filtration rate in affected kidneys. To determine if volume depletion augments this response, we compared the effects of captopril, furosemide, and combined furosemide plus captopril on individual kidney computer-derived clearances of 99mTc-diethylenetriamine pentaacetic acid (DTPA) and [131I]o-iodohippurate in two-kidney, one clip Goldblatt hypertensive rats and normal controls. In clipped kidneys, captopril reduced DTPA clearance significantly from baseline (from 0.31 +/- 0.02 to 0.19 +/- 0.04 ml/min/100 g; p less than 0.02) whereas furosemide alone had no effect (0.28 +/- 0.03 ml/min/100 g). Combined furosemide plus captopril further reduced clipped kidney DTPA clearance to a level significantly less than captopril alone (0.10 +/- 0.02 ml/min/100 g; p less than 0.02). Clipped kidney o-iodohippurate clearance was not changed from baseline by any treatment. In contralateral unclipped and normal kidneys, DTPA clearance did not decline from baseline following either captopril or furosemide plus captopril treatment. Since the dose of captopril used (3 mg/kg by intraperitoneal injection) did not reduce systolic blood pressure of hypertensive rats significantly, these changes probably reflect intrarenal rather than systemic hemodynamic effects of converting enzyme inhibition and are consistent with the hypothesis that captopril interferes with glomerular filtration in stenotic kidneys by reducing efferent arteriolar vascular resistance. Prior volume depletion accentuates the effect of captopril on stenotic kidney glomerular filtration rate, providing improved functional discrimination of stenotic kidneys from contralateral unclipped and normal kidneys. These results indicate that furosemide-induced volume depletion may increase the diagnostic sensitivity of captopril-enhanced 99mTc-DTPA renography in the detection of unilateral renovascular hypertension.

Immunoreactivity of 111In and 131I fibrin-specific monoclonal antibody used for thrombus imaging.

Immunoreactivity of radiolabeled F(ab')2 fragment of anti-fibrin T2G1s monoclonal antibody was determined by affinity chromatography using fibrin-coated Sepharose. This preparation is useful for thrombus detection in vivo by gamma camera imaging, provided a high percentage of immunoreactivity is retained after labeling. For 111In labeling, DTPA/F(ab')2 molar ratios were varied from 1000 to 6600/1, with little effect on immunoreactivity. Immunoreactivity of the F(ab')2 fragment, labeled with imaging doses of 131I and 111In, remained high and ranged from 81% to 89%. Equilibrium binding analysis determined the affinity constants of 111In- or 125I-labeled T2G1s and its F(ab')2 and Fab fragments, to be equivalent (Kd approximately 3 X 10(-8) M). This suggests that only one binding domain of T2G1s binds to fibrin even though there are two antigenic sites/mol of fibrin.

Cellular radiation doses of labeled neutrophils and platelets.

Radiation doses were calculated for human neutrophils and platelets labeled by phosphorus-32, chromium-51, gallium-67, technetium-99m, indium-111, and mercury-197. The cells were assumed to be spheres with radii of 4.87 microm and 1.07 microm, respectively, with all the radioactivity at either the center or uniformly distributed on the surface. Surprisingly high dose rates were found, due primarily to the small mass and therefore high radioactive concentration and to low-energy electrons, such as Auger electrons. Average total doses to these cells during their effective lifetime in the blood are presented.

Survey of radioactive agents for in vitro labeling of phagocytic leukocytes. I. Soluble agents.

Twenty-three soluble (nonparticulate) radioactive agents were screened for their ability to label leukocytes in vitro in the presence or absence of plasma and red cells. The degree of cell binding was compared with that of other agents previously reported. Leukocyte binding of 2% or more of the added radioactivity was obtained with ten of these agents. High labeling yields were obtained only with nonpolar lipid-soluble complexes capable of penetrating lipid cell membranes. Unfortunately, this type of labeling tends to be reduced by plasma protein. Some lipophilic radioactive agents tend to elute from the cells after labeling. Compared with radioactive particles, soluble radiopharmaceuticals offer the advantage of easy centrifugal separation of the cell-bound from the residual activity in the suspension fluid. However, the labeling yield tends to be lower than for radioactive particles, and other cellular elements are labeled in addition to the phagocytic leukocytes. In this survey, the most promising soluble agents were 111In or 99mTc complexes of oxine, 111In-tetraphenylporphyrin, DNA labeled with radioactive iodine, and DNA labeled with 77Br and complexed with adriamycin. The ultimate value of any of these agents must await adequate in vivo testing in experimental animals and clinical trials.

Survey of radioactive agents for in vitro labeling of phagocytic leukocytes. II. Particles.

When various radioactive particles are incubated and tumbled in concentrated suspensions of blood phagocytes at body temperature for 1 hr, they bind to the phagocytic cells with a labeling yield of 30-40%. In vitro experiments show that, for some radioactive colloids, a sizeable fraction of the total cellular binding results from nonspecific surface adsorption to other cells and from reversible surface adsorption to phagocytes without engulfment. No completely satisfactory in vitro methods have been found for separating leukocytes with completely engulfed particles from those with surface-adherent particles; nonetheless, surface adherence can be partially reversed by 20% acid citrate dextrose (ACD) solution or by an excess of nonradioactive colloid. Gelatinization of colloidal particles tends to increase their binding to phagocytic cells but also increases the degree of nonspecific adherence to other cells. Technetium-99m-millimicrospheres, 0.5-2 mum in diameter, are optimal in size for phagocytosis by neutrophils, and their non-specific adherence to other cells is minimal. Because of the microspheres' poor stability in aqueous suspension, however, it is technically difficult to separate free from phagocytosed radioactivity after cell incubation. The highly stable small-particle colloids (less than 0.1 mum), such as 198Au-colloid or 111In-colloid without iron carrier, are phagocytosed poorly or not at all by neutrophils, although they are engulfed by mononuclear cells.

The localization of indium-111-leukocytes, gallium-67-polyclonal IgG and other radioactive agents in acute focal inflammatory lesions.

A variety of radioactive agents, injected directly intravenously have demonstrated foci of inflammation by gamma camera imaging, avoiding the in vitro preparation of labeled leukocytes. This study sought to find out if any of these agents mimicked the biodistribution in abscesses and non-target organs of labeled mixed leukocyte suspensions. Eight different agents were compared with 111In-oxine labeled leukocytes in an acute soft tissue E. coli abscess and an acute arthritic lesion in 24 dogs one day after intravenous administration. These included 67Ga-citrate, human and canine polyclonal immunoglobulin (IgG), rabbit anti-dog polyclonal IgG, serum albumin, monoclonal antibody TNT-1 F(ab')2 against nuclear antigens, 57Co-porphyrin and serum albumin nanocolloid. None of these agents achieved abscess concentrations approaching those obtained with labeled leukocytes, and their abscess/blood and abscess/muscle concentration ratios were considerably lower. No statistically significant differences were found between the different radiolabeled proteins evaluated. The abscess concentration of 99mTc-nanocolloid was much lower than that of other agents, and the results with the oldest agent, 67Ga-citrate, were disappointing in these acute experiments.

Indium-113m-labeled polyfunctional phosphonates as bone-imaging agents.

Indium-113m complexed with polyfunctional phosphonates EDTMP (an analog of EDTA with carboxylic groups replaced by phosphate groups) and DTPMP (an analog of DTPA) showed preferential skeletal localization in experimental animals. Excellent images of the rabbit skeleton were obtained with both 113mIn and 111In complexes using the scintillation camera. In tissue radioassay using 85Sr as a simultaneous biologic standard, 113mIn-EDTMP compound showed higher concentration in the skeleton than the DTPMP complex and its bone uptake was comparable to that of 85Sr. Renal excretion was greater for the DTPMP complex (70% vs. 50% for EDTMP at 4 hr) and its blood clearance was faster than EDTMP. EDTMP was found to be the superior agent also to two other polyfunctional phosphonates, NTMP and HMDTMP. Because of the excellent skeletal localization with minimal soft-tissue levels, 113mIn-EDTMP may find use in bone scanning in humans wherever 99mTc bone-imaging agents are not available. These compounds may prove useful also in demonstrating acute myocardial infarcts, particularly for repeat studies after 99mTc bone agents have already been administered.

Comparison of different radioactive agents for the detection of renovascular hypertension with captopril in a rat model.

In Goldblatt hypertension in rats produced by implanting a silver clip on the left renal artery, captopril induces a greater difference in the 1-min uptake of diethylenetriaminepentaacetic acid (DTPA) between the two kidneys than in baseline uptakes, similar to the experiences in unilateral renovascular hypertension in man. The combination of captopril and furosemide induces an even greater difference in renal uptakes than with captopril alone in this rat model. In paired experiments, DTPA complexes were used as a standard to compare the differences in renal uptake between the two kidneys after captopril-furosemide with other existing and potential renal radiodiagnostic agents. No statistically significant difference was found between DTPA, glucoheptonate, dimercaptosuccinic acid, aminated dextran, or lysozyme. However, the differences in renal uptake were significantly less with hippuran than with DTPA. Furosemide and captopril caused delayed renal retention of hippuran after one minute. This response appeared to be due to non-specific volume depletion because it occurred in both clipped and unclipped kidneys.

Evaluation of cyclosporine nephrotoxicity in rats with various renal radioactive agents.

The efficacy of different radiodiagnostic agents for demonstrating the decline in renal function from cyclosporine (CyA) nephrotoxicity was assessed in rats receiving a standard dose of the drug for 2 wk, compared with control rats. The agents included [99mTc]DTPA, [131I]hippuran, [111In]lysozyme, [99mTc]glucoheptonate (GHA), [99mTc]dimercaptosuccinate (DMS) and [111In]aminated dextran (amdex). A small dose of [99mTc]- or [111In]DTPA was administered simultaneously to normalize the results for variations in drug response from one animal to another. There were statistically significant differences in the detectability of the renal functional impairment by plasma clearance, early and 2-hr renal uptake among the different agents. However, none was clearly superior to DTPA. This conclusion is consistent with previous studies which showed a parallel decline in glomerular filtration rate (GFR) and effective renal plasma flow in acute CyA toxicity probably due primarily to vasoconstriction.

Diagnosis of angiotensinogenic hypertension: the complementary roles of renal scintigraphy and the saralasin infusion test.

A recently developed 1-day screening procedure for angiotensinogenic ("high-renin") hypertension is based on (A) a fall in blood pressure in response to intravenous infusion of the angiotensin antagonist, saralasin (P-113), and (B) peripheral venous renin assays by radioimmunoassay, in a sodium-depleted state. Out of 700 hypertensive patients screened by these tests, 160 had renal imaging performed with technetium-99m glucoheptonate and iodine-131 Hippuran. The P-113 infusion test proved superior to peripheral venous renin assays for the detection of angiotensinogenic hypertension. Positive infusion tests correlated well with renal vein renin assays. Frequently, however, both these tests were positive with bilateral renal disease and/or malignant hypertension. While renal imaging proved valuable in indicating which patients had a unilateral abnormality, it frequently could not distinguish unilateral renovascular disease from unilateral parenchymal disease unrelated to angiotensinogenic hypertension. Twenty-five patients in this series had arteriographic renal artery stenosis, of whom 3 had false negative P-113 infusion tests, 9 had negative peripheral renin assays, and 3 had no imaging abnormalities. This study indicates that scintigraphy is a useful procedure for the investigation of hypertensive patients when the initial P-113 infusion test is positive, or discordant with other findings. By imaging, angiotensinogenic hypertension due to bilateral renal disease can be distinguished from unilateral renovascular disease, and the site of the ischemic renal tissue can usually be identified.

Detection of diffuse glomerular lesions in rats: I. Comparisons of conventional radioactive agents.

Conventional renal diagnostic agents, [131I]hippuran, [99mTc]glucoheptonate (GHA), and [99mTc] dimercaptosuccinate (DMS) were compared with [99mTc] or [111In] diethylenetriaminepentaacetic (DTPA) for the detection of glomerular damage in rats compared with controls. The glomerular lesions were induced by the i.v. injection of puromycin aminonucleoside (PA) 9 days before the radionuclide studies, a model of spontaneous "minimal change" glomerulonephritis in humans. Computer-generated early renal uptake of [99mTc]DTPA or GHA correlated with the glomerular filtration rate (GFR) quantitated by biexponential plasma clearance of DTPA administered by single i.v. injection. The early renal uptake of hippuran and DMS correlated poorly with GFR as assessed by DTPA clearance. However, the 2-hr renal retention of DMS correlated well with the DTPA clearance. None of the parameters measured with [131I]hippuran correlated well with DTPA clearance, probably because of decreased protein plasma binding of hippuran secondary to hypoproteinemia in this experimental model. It was concluded that none of these agents was superior to labeled DTPA for the detection of glomerular damage in this experimental model.

Comparison of different radioactive renal agents in cisplatin-induced tubular toxicity in rats.

The efficacy of five different radiodiagnostic agents for detecting renal tubular dysfunction induced with cisplatin in rats was compared to controls. Diethylenetriaminepentaacetic acid (DTPA) labeled with 99mTc or 111In was administered simultaneously with each of the other four agents [99mTc]glucoheptonate, [99mTc]dimercaptosuccinic acid, [131I]hippuran and [111In]lysozyme) as a standard to normalize for differences in functional impairment from animal to animal from the same dose of cisplatin. The 2-hr plasma clearance and computer-generated 2- to 3-min uptake in the two kidneys with [99mTc]dimercaptosuccinic acid were significantly inferior to similar measurements with the other agents in differentiating abnormal from normal function. The 2-hr uptake of [99mTc]glucoheptonate and [111In]lysozyme proved of no value in this differentiation. The late renal retention of [99mTc]dimercaptosuccinic acid well separated the cisplatin from control rats, but the greatest difference was observed by the 2-hr uptakes of [131I]hippuran and DTPA.

Technetium-99m-methylene diphosphonate--a superior agent for skeletal imaging: comparison with other technetium complexes.

Methylene diphosphonate (MDP) was formulated as a complex of 99mTc for skeletal imaging. This agent was compared with three other bone-seeking technetium agents: ethane-1-hydroxy-1, 1-diphosphonate (EHDP), pyrophosphate, and polyphosphate. In tissue radioassay experiments in rodents, the technetium complexes of MDP and EHDP were similar, but skeletal concentration with both of these agents was higher than that with pyrophosphate or polyphosphate. The total-body retention of MDP and EHDP complexed with 95mTc was studied in beagle dogs for 35 days by excretion measurements and total-body counting and compared with polyphosphate and pertechnetate. The long-term retention was greater for MDP. The 5-day cumulative fecal excretion of 95mTc was low when administered as EHDP or polyphosphate complexes and negligible when administered as MDP complex. In six human volunteers the blood clearance of 99mTc-mdp was similar to that of 18F and significantly faster than that of 99mTc-EHDP. Pyrophosphate cleared from the blood much faster than polyphosphate but slower than the diphosphonates. The urinary excretion of the MDP complex was greater than for EHDP within the first 2-3 hr after injection. The 24-hr urinary excretion of pyrophosphate and polyphosphate complexes was not as complete as for the diphosphonates. All four 99mTc complexes proved satisfactory for clinical imaging studies. The MDP complex produced images of superior quality as early as 2 hr after administration, attributable to its more rapid clearance from the blood and soft tissues. On the contrary, a longer interval of 3-4 hr after injection was usually needed for 99mTc-EHDP; pyrophosphate and polyphosphate complexes regularly required a waiting period of 4 hr. Comparitive radiation dose estimates were made based on the available biologic distribution data for these 99mTc skeletal-localizing agents.