Swelling of Doubly Magic

Interaction cross sections for ^{42-51}Ca on a carbon target at 280 MeV/nucleon have been measured for the first time. The neutron number dependence of derived root-mean-square matter radii shows a significant increase beyond the neutron magic number N=28. Furthermore, this enhancement of matter radii is much larger than that of the previously measured charge radii, indicating a novel growth in neutron skin thickness. A simple examination based on the Fermi-type distribution, and mean field calculations point out that this anomalous enhancement of the nuclear size beyond N=28 results from an enlargement of the core by a sudden increase in the surface diffuseness of the neutron density distribution, which implies the swelling of the bare ^{48}Ca core in Ca isotopes beyond N=28.

Impact of antihypertensive medication adherence on blood pressure control in hypertension: the COMFORT study.

BACKGROUND: It has not been fully elucidated whether antihypertensive medication adherence affects blood pressure (BP) control in hypertension cases. AIM: To investigate the association of adherence to antihypertensive drug regimens and BP control using data from the Combination Pill of Losartan Potassium and Hydrochlorothiazide for Improvement of Medication Compliance Trial (COMFORT) study. DESIGN: An observational analysis from a randomized controlled trial. METHODS: A total of 203 hypertensive subjects were randomly assigned to a daily regimen of a combination pill (losartan 50 mg/hydrochlorothiazide 12.5 mg) or two pills, an angiotensin II receptor blocker and a thiazide diuretic. Medication adherence calculated based on pill counts and BPs was evaluated at 1, 3 and 6 months after randomization. RESULTS: The subjects were divided into three groups according to their adherence, i.e. relatively low-adherence (<90%; n = 19), moderate-adherence (90-99%; n = 71) and high-adherence (100%; n = 113) groups. Clinical characteristics of the subjects including BP, sex, randomized treatments and past medical history did not differ significantly among the three groups. Achieved follow-up BPs over the 6-month treatment period, which were adjusted for age, sex, baseline BP and randomized treatment, were significantly higher in the low-adherence group (135/78 mmHg) compared with the high-adherence (130/74 mmHg; P = 0.02/0.02) and the moderate-adherence (128/74 mmHg; P = 0.003/0.02) groups. CONCLUSION: Low adherence to an antihypertensive-drug regimen was associated with poor BP control.

Direct observation of long-lived isomers in 212Bi.

Long-lived isomers in (212)Bi have been studied following (238)U projectile fragmentation at 670 MeV per nucleon. The fragmentation products were injected as highly charged ions into a storage ring, giving access to masses and half-lives. While the excitation energy of the first isomer of (212)Bi was confirmed, the second isomer was observed at 1478(30) keV, in contrast to the previously accepted value of >1910 keV. It was also found to have an extended Lorentz-corrected in-ring half-life >30 min, compared to 7.0(3) min for the neutral atom. Both the energy and half-life differences can be understood as being due a substantial, though previously unrecognized, internal decay branch for neutral atoms. Earlier shell-model calculations are now found to give good agreement with the isomer excitation energy. Furthermore, these and new calculations predict the existence of states at slightly higher energy that could facilitate isomer deexcitation studies.

Magnetic dipole moment of the doubly-closed-shell plus one proton nucleus 49Sc.

The nucleus 49Sc, having a single f(7/2) proton outside doubly magic 48Ca (Z=20, N=28), is one of the very few isotopes which makes possible testing of the fundamental theory of nuclear magnetism. The magnetic moment has been measured by online ß NMR of nuclei oriented at milli-Kelvin temperatures to be (+)5.616(25) µ(N). The result is discussed in terms of a detailed theory of the structure of the magnetic moment operator, showing excellent agreement with calculated departure from the f(7/2) Schmidt limit extreme single-particle value. The measurement completes the sequence of moments of Sc isotopes with even numbers of f(7/2) neutrons: the first such isotopic chain between two major shells for which a full set of moment measurements exists. The result further completes the isotonic sequence of ground-state moments of nuclei with an odd number of f(7/2) protons coupled to a closed subshell of f(7/2) neutrons. Comparison with a recent shell-model calculation of the latter sequence is made.

Observation of a large reaction cross section in the drip-line nucleus 22C.

Reaction cross sections (sigma(R)) for 19C, 20C and the drip-line nucleus 22C on a liquid hydrogen target have been measured at around 40A MeV by a transmission method. A large enhancement of sigma(R) for 22C compared to those for neighboring C isotopes was observed. Using a finite-range Glauber calculation under an optical-limit approximation the rms matter radius of 22C was deduced to be 5.4+/-0.9 fm. It does not follow the systematic behavior of radii in carbon isotopes with N < or = 14, suggesting a neutron halo. It was found by an analysis based on a few-body Glauber calculation that the two-valence neutrons in 22C preferentially occupy the 1s(1/2) orbital.

Schottky mass measurement of the 208Hg isotope: implication for the proton-neutron interaction strength around doubly magic 208Pb.

Time-resolved Schottky mass spectrometry has been applied to uranium projectile fragments which yielded the mass value for the 208Hg (Z=80, N=128) isotope. The mass excess value of ME=-13 265(31) keV has been obtained, which has been used to determine the proton-neutron interaction strength in 210Pb, as a double difference of atomic masses. The results show a dramatic variation of the strength for lead isotopes when crossing the N=126 neutron shell closure, thus confirming the empirical predictions that this interaction strength is sensitive to the overlap of the wave functions of the last valence neutrons and protons.

Simultaneous measurement of beta- decay to bound and continuum electron states.

We report the first measurement of a ratio lambda(beta(b))/lambda(beta(c)) of bound-state ((lambda(beta(b))) and continuum-state (lambda(beta(c))) beta(-)-decay rates for the case of bare 207Tl81+ ions. These ions were produced at the GSI fragment separator FRS by projectile fragmentation of a 208Pb beam. After in-flight separation with the Brho-deltaE-Brho method, they were injected into the experimental storage-ring ESR at an energy of 400.5A MeV, stored, and electron cooled. The number of both the 207Tl81+ ions and their bound-state beta(-)-decay daughters, hydrogen-like 207Pb81+ ions, were measured as a function of storage time by recording their Schottky-noise intensities. The experimental result, lambda(beta(b))/lambda(beta(c)) = 0.188(18), is in very good agreement with the value of 0.171(1) obtained from theory employing spectra of allowed transitions.

Shell structure of the near-dripline nucleus 23O.

Breakup reactions were used to study the ground-state configuration of the neutron-rich isotope 23O. The 22O fragments produced in one-nucleon removal from 23O at 938 MeV/nucleon in a carbon target were detected in coincidence with deexciting gamma rays. The widths of the longitudinal momentum distributions of the 22O fragments and the one-neutron removal cross sections were interpreted in the framework of a simple theoretical model which favors the assignment of Ipi = 1/2+ to the 23O ground state.

Precision spectroscopy of pionic 1s states of Sn nuclei and evidence for partial restoration of chiral symmetry in the nuclear medium.

Deeply bound 1s states of pi(-) in (115,119,123)Sn were preferentially observed using the Sn(d,3He) pion-transfer reaction under the recoil-free condition. The 1s binding energies and widths were precisely determined and were used to deduce the isovector parameter of the s-wave pion-nucleus potential to be b1=-(0.115+/-0.007)m(-1)(pi). The observed enhancement of |b(1)| over the free piN value (b(free)1/b1=0.78+/-0.05) indicates a reduction of the chiral order parameter, f*pi(rho)2/f2pi approximately 0.64, at the normal nuclear density, rho=rho(0).

MRI of cortical dysplasia--correlation with pathological findings.

Cortical dysplasia (CD) is the most epileptogenic structural lesion associated with epilepsy and patients with intractable seizures caused by this condition are good surgical candidates. MRI plays an important role in detecting the abnormalities of CD. We clarified the MRI characteristics of CD by comparing imaging and histological findings in 20 patients with intractable seizures who underwent surgical resection. There were 12 males and eight females, mean age at operation was 15 years. MRI was performed at 1.5 tesla; T1-weighted, T2- and proton density-weighted spin-echo and fluid-attenuated inversion-recovery (FLAIR) images were obtained. The lesions were in the frontal lobe in nine cases, temporal in two, occipital in another two, insular in one and multilobar in six. Blurring of the grey/white matter junction was seen in all patients, and T2 prolongation in white matter and/or at the grey/white matter junction in 19. Abnormal signal intensity was more frequent in the white matter or at the grey/white matter junction than in the grey matter. FLAIR images made this abnormal high signal easier to appreciate, and we thought them very useful in this context. In areas of T2 prolongation, we saw dysplastic neurones and/or balloon cells, dysmyelination, and ectopic neuronal clustering histologically; glial proliferation played an important role in prolonging T2.

Doxorubicin ototoxicity is induced in mice by combination treatment with cyclosporin A.

Although doxorubicin [adriamycin (ADM)] ototoxicity has not been detected to date, it has been reported that neurotoxicity in the central nervous system was induced by chemotherapy with ADM in patients receiving chronic cyclosporin A (CsA) treatment. ADM ototoxicity may be induced by combination therapy with CsA because extrusion of ADM from the inner ear by p-glycoprotein (p-gp), which acts as an extrusion pump and is expressed on the surface of endothelial cells of capillary blood vessels, might be inhibited by CsA. resulting in significant accumulation of ADM in the inner ear. ADM (10 mg/kg) was administered to FVB mice either with or without CsA (200 mg/kg). Auditory brainstem responses (ABRs) were recorded before and after treatment. ABR changes were not observed in mice treated with either ADM or CsA alone. Threshold elevation, elongation of wave I-V latencies and interpeak latencies of waves I-II, I-III, I-IV and I-V were detected in mice treated with ADM in combination with CsA. These changes reached their peak values 3 weeks after treatment, and then recovered to pre-treatment levels. In normal mice, ADM is extruded by p-gp from the inner ear and auditory pathway, thus preventing hearing disorder. However, ADM ototoxicity was induced by combination therapy with CsA, indicating that CsA has an inhibitory action on p-gp function in the auditory pathway, including the inner ear. After organ transplantation, therefore, clinical administration of ADM in combination with CsA should be performed with caution.

Intraoperative identification of regenerated chorda tympani nerve and its relationship to recovered taste function.

This study demonstrated a simple method of repairing the severed chorda tympani nerve and a method of intraoperative identification of regenerated nerves, and evaluated taste function of regenerated nerves. Seven patients who underwent staged tympanoplasty and whose chorda tympani nerve was severed during primary surgery were evaluated. When the chorda tympani nerve was severed during primary surgery, proximal and distal stumps were anastomosed or approximated almost in the original position and fixed with fibrin glue on the temporal muscle fascia used to reconstruct the eardrum by the underlay method. During primary surgery, end-to-end anastomosis was possible in 3 patients but nerve gap defects remained in the other 4 patients. In all 7 patients, regenerated nerves were identified during secondary surgery not in the tympanic cavity but in the submucosal layer of the previously reconstructed eardrum. In all patients, complete or incomplete recovery of taste perception was observed by both the filter paper disk method and electrogustometry, suggesting that the regenerated nerves had actual taste function. From these results, it was concluded that the severed chorda tympani nerve could regenerate in the reconstructed eardrum even if nerve gap defects remained between the proximal and distal cut ends, when repair or approximation of the nerve was properly completed.

Homozygous disruption of the mdrla P-glycoprotein gene affects blood-nerve barrier function in mice administered with neurotoxic drugs.

We investigated the expression and function of mdr1a p-glycoprotein in peripheral nerves, including the VIIth and VIIIth nerves, using mdr1a p-glycoprotein gene knockout mice [mdr1a(-/-) mice] and wild-type mdr1a(+/+) mice. P-glycoprotein expression in capillary endothelial cells of the peripheral nerve tissues was detected by immunohistochemical and RT-PCR analyses in mdr1a(+/+) mice but not in mdr1a(-/-) mice. Pharmacokinetic analyses indicated that, compared to mdr1a(+/+) mice, mdr1a(-/-) mice showed a significantly higher accumulation of p-glycoprotein substrate drugs such as vinblastine and doxorubicin, which are neurotoxic. Tissue concentrations of vinblastine and doxorubicin were lower in the order of the brain, peripheral nerves and most other organs. However, increased accumulation was not detected after administering another neurotoxic drug, cisplatin, indicating that p-glycoprotein is selective at extruding drugs. These data indicate that mdr1a p-glycoprotein, which acts as an efflux pump, might play an important role in the blood-nerve barrier to prevent side effects induced by neurotoxic p-glycoprotein substrate drugs. The participation of p-glycoprotein in the blood-nerve barrier is considered to represent a new functional mechanism of this barrier.

Effectiveness of systematized hepatectomy with Glisson's pedicle transection at the hepatic hilus for small nodular hepatocellular carcinoma: retrospective analysis.

BACKGROUND: The effectiveness of systematized hepatectomy with transection of Glisson's pedicle at the hepatic hilus in patients with small nodular hepatocellular carcinoma (HCC) has not been confirmed. METHODS: Surgical outcomes were reviewed in 204 patients with single nodular HCCs less than 5 cm in greatest diameter, including 68 patients with tumors that showed extranodular growth and 136 patients with tumors that did not, who had undergone curative hepatectomy (partial hepatic resection, n = 114; systematized hepatectomy, n = 90) from 1990 through 1994. RESULTS: The rates of microscopic vascular invasion and intrahepatic metastasis were significantly higher in patients who had single nodular HCCs with extranodular growth (34% and 49%) than in patients who had single nodular HCCs without extranodular growth (13%, P =.001, and 4%, P <.001). The 5-year survival rate in patients who had single nodular HCCs with extranodular growth was significantly greater after systematized hepatectomy (67%) than after partial hepatic resection (21%, P =.0002). Multivariate analysis showed that the type of operation was an independent prognostic factor in patients with single nodular HCCs with extranodular growth (P =.0008). CONCLUSIONS: Systematized hepatectomy with Glisson's pedicle transection at the hepatic hilus should be performed in patients who have single small nodular HCCs with extranodular growth because these tumors often invade within the liver sector containing the tumor.

Modification of thermosensitivity and chemosensitivity induced by combined treatments with hyperthermia and adriamycin.

Both adriamycin (ADM) and hyperthermia show thermal chemo-enhancement. Tolerance induction against ADM in heated cells has been reported resulting in clinical difficulty of cancer therapy. We investigated thermo-enhancement induced with ADM (0.2 microg/ml) treatment alone or combined with ADM and 42 degrees C hyperthermia in Chinese hamster V79 cells in vitro. Intracellular accumulation of hsc70 and hsp72 proteins after hyperthermia or ADM was observed to examine the possible relationship between cell killing effect and their accumulations. Thermosensitivity of V79 cells at 42 degrees C after the simultaneous treatments with ADM showed marked thermo-enhancement within the short-term treatments for less than 1 h, while the combined treatments for longer than 1 h, the cells showed reduced thermosensitivity. Survival from the simultaneous treatments for less than 1 h was reduced markedly less than the single treatment both with ADM or 42 degrees C hyperthermia alone. Thermotolerance was markedly induced in a step-up hyperthermia (42 degrees C 2 h-44 degrees C). The combined treatments with ADM and 44 degrees C hyperthermia following the 42 degrees C preheating alone does not inhibit thermotolerance development. The combined treatments with ADM and 42 degrees C preheating showed markedly interactive cell killing, but no thermo-enhancement to the following 44 degrees C hyperthermia was shown. The leveling slope of the 44 degrees C heating period-survival curve was drawn. In the Western blot analyses, hsc70 existed constitutively in the V79 cells. Following the 42 or 44 degrees C hyperthermia alone, intracellular accumulation of hsp72 was determined. ADM treatment alone did not induce any accumulation of hsp72. In the simultaneous treatments with ADM and hyperthermia, the accumulation of hsp72 was markedly reduced. The accumulation of hsp72 after the combined treatment with ADM and hyperthermia was not observed as markedly as that after hyperthermia alone.

Enhancement of cell killing by induction of apoptosis after treatment with mild hyperthermia at 42 degrees C and cisplatin.

Ohtsubo, T., Igawa, H., Saito, T., Matsumoto, H., Park, H. J., Song, C. W., Kano, E. and Saito, H. Enhancement of Cell Killing by Induction of Apoptosis after Treatment with Mild Hyperthermia at 42 degrees C and Cisplatin. Radiat. Res. 156, 103-109 (2001). We examined the interactive effects of cisplatin (1.0 microg/ml) combined with hyperthermia on cell killing and on the induction of apoptosis in IMC-3 human maxillary carcinoma cells. The cytotoxic effects of hyperthermia on IMC-3 cells at 44 degrees C were greater than at 42 degrees C, as has been reported for many other cells. The induction of apoptosis, DNA fragmentation and poly(ADP-ribose) polymerase cleavage were greater after hyperthermia at 44 degrees C for 30 min compared with treatment at 42 degrees C for 105 min, even though both of these heat doses were isoeffective in reducing cell survival to 50%. Treatment with cisplatin at 37 degrees C for up to 120 min did not result in cytotoxicity or the induction of apoptosis. The enhancement ratio for treatment with cisplatin at 42 degrees C was greater than that at 44 degrees C. More apoptosis was induced after the treatment with cisplatin at 42 degrees C compared to treatment with cisplatin at 44 degrees C. Taking these findings together, the combination of cisplatin and hyperthermia at 42 degrees C appeared to be more effective than cisplatin with hyperthermia at 44 degrees C for the induction of apoptosis in IMC-3 cells.

Cyclosporin A inhibits the extrusion pump function of p-glycoprotein in the inner ear of mice treated with vinblastine and doxorubicin.

Cyclosporin A (CsA) inhibits the membrane transport protein p-glycoprotein (p-gp) and can enhance the accumulation of vinblastine (VBL) and doxorubicin (Dx) in the inner ear of mice. In mice pretreated with 200 mg/kg of CsA, there were significantly increased VBL and Dx concentrations detected in the inner ear tissue and other organs, with a small but significant increase in the brain. Furthermore, hearing thresholds measured by auditory brainstem responses were significantly elevated 3 weeks after VBL or Dx treatment in combination with CsA. However, the altered thresholds recovered to pretreatment levels 8 weeks after treatment. Pharmacokinetic and functional alterations observed in this study suggest caution in applying these combinations in clinical practice.

Acidic environment modifies heat- or radiation-induced apoptosis in human maxillary cancer cells.

PURPOSE: The effects of hyperthermia or irradiation on cell killing and induction of apoptosis were evaluated using human maxillary carcinoma IMC-3 cells and low pH (pH 6.8) adapted cells (IMC-3-pH). METHODS AND MATERIALS: Cellular heat-sensitivity or radiosensitivity was determined using the clonogenic assay. Apoptosis was assessed on the basis of a flow cytometric determination of the DNA content, DNA fragmentation, and poly(ADP-ribose)polymerase cleavage. RESULTS: When IMC-3 cells or IMC-3-pH cells were exposed to heat at 44 degrees C in pH 6.8 medium, an increase in thermosensitivity was observed compared with when the IMC-3 cells were exposed to heat at 44 degrees C in pH 7.4 medium. However, the selective reduction in survival was not observed after irradiation. In IMC-3 cells, apoptosis after heating at 44 degrees C for 60 min in pH 7.4 medium occurred earlier than that after 8 Gy irradiation, although both thermal and irradiated doses decreased the cell count to 10%. The degree of apoptosis after heating at pH 6.8 in IMC-3 cells or IMC-3-pH cells was greater than that at pH 7.4 in IMC-3 cells. However, the degree of apoptosis after 8 Gy irradiation at pH 6.8 in IMC-3 cells or IMC-3-pH cells was smaller than that at pH 7.4 in IMC-3 cells. CONCLUSION: Hyperthermia treatment is more effective at inducing apoptosis than radiation is in tumors that contain a population of low pH adapted cells.