First Determination of the Level Structure of an sd-Shell Hypernucleus, _{Λ}

We report on the first observation of γ rays emitted from an sd-shell hypernucleus, _{Λ}^{19}F. The energy spacing between the ground state doublet, 1/2^{+} and 3/2^{+} states, of _{Λ}^{19}F is determined to be 315.5±0.4(stat)_{-0.5}^{+0.6}(syst) keV by measuring the γ-ray energy of the M1(3/2^{+}→1/2^{+}) transition. In addition, three γ-ray peaks are observed and assigned as E2(5/2^{+}→1/2^{+}), E1(1/2^{-}→1/2^{+}), and E1(1/2^{-}→3/2^{+}) transitions. The excitation energies of the 5/2^{+} and 1/2^{-} states are determined to be 895.2±0.3(stat)±0.5(syst) and 1265.6±1.2(stat)_{-0.5}^{+0.7}(syst) keV, respectively. It is found that the ground state doublet spacing is well described by theoretical models based on existing s- and p-shell hypernuclear data.

Measurement of Excitation Spectra in the

Excitation spectra of ^{11}C are measured in the ^{12}C(p,d) reaction near the η^{'} emission threshold. A proton beam extracted from the synchrotron SIS-18 at GSI with an incident energy of 2.5 GeV impinges on a carbon target. The momenta of deuterons emitted at 0° are precisely measured with the fragment separator (FRS) operated as a spectrometer. In contrast to theoretical predictions on the possible existence of deeply bound η^{'}-mesic states in carbon nuclei, no distinct structures are observed associated with the formation of bound states. The spectra are analyzed to set stringent constraints on the formation cross section and on the hitherto barely known η^{'}-nucleus interaction.

Experimental review of hypernuclear physics: recent achievements and future perspectives.

Since the shutdown of several old proton synchrotrons, which played a fundamental role in the second generation experiments in hypernuclear physics performed in Europe, USA and Japan, some new experimental setups aiming to achieve sub-MeV energy resolution have been operating for a long time. Over the last decade the hypernuclear physics community has been committed to carrying out several third generation experiments by exploiting the potential offered by new accelerators, such as a continuous electron beam machine and a ϕ-factory. Large data samples were collected on specific items thanks to dedicated facilities and experimental apparatuses. The attention was mainly focused on both high-resolution spectroscopy and the decay mode study of single Λ-hypernuclei. Nowadays this phase is over but, until recently, important and, to some extent, unexpected results were achieved. An updated review of selected experimental results is presented, as well as a survey of perspectives for future studies.

Observation of Spin-Dependent Charge Symmetry Breaking in ΛN Interaction: Gamma-Ray Spectroscopy of _{Λ}

The energy spacing between the spin-doublet bound state of _{Λ}^{4}He(1^{+},0^{+}) was determined to be 1406±2±2 keV, by measuring γ rays for the 1^{+}→0^{+} transition with a high efficiency germanium detector array in coincidence with the ^{4}He(K^{-},π^{-})_{Λ}^{4}He reaction at J-PARC. In comparison to the corresponding energy spacing in the mirror hypernucleus _{Λ}^{4}H, the present result clearly indicates the existence of charge symmetry breaking (CSB) in ΛN interaction. By combining the energy spacings with the known ground-state binding energies, it is also found that the CSB effect is large in the 0^{+} ground state but is vanishingly small in the 1^{+} excited state, demonstrating that the ΛN CSB interaction has spin dependence.

Evidence for heavy hyperhydrogen (Λ)(6)h.

Evidence for the neutron-rich hypernucleus (Λ)(6)H is presented from the FINUDA experiment at DAΦNE, Frascati, studying (π+,π-) pairs in coincidence from the K(stop)(-) + (6)Li →(Λ)(6)H + π+ production reaction followed by (Λ)(6)H → (6)He + π- weak decay. The production rate of (Λ)(6) undergoing this two-body π- decay is determined to be (2.9 ± 2.0) × 10(-6)/K(stop)(-). Its binding energy, evaluated jointly from production and decay, is BΛ((Λ)(6)H) = (4.0 ± 1.1) MeV with respect to (5)H+Λ. A systematic difference of (0.98 ± 0.74) MeV between BΛ values derived separately from decay and from production is tentatively assigned to the (Λ)(6)H 0(g.s.)(+) → 1+ excitation.

Search for the Θ+ pentaquark via the π(-)p→K(-)X reaction at 1.92 GeV/c.

The Θ(+) pentaquark baryon was searched for via the π(-)p→K(-)X reaction with a missing mass resolution of 1.4 MeV/c(2) (FWHM) at the Japan Proton Accelerator Research Complex (J-PARC). π(-) meson beams were incident on the liquid hydrogen target with a beam momentum of 1.92 GeV/c. No peak structure corresponding to the Θ(+) mass was observed. The upper limit of the production cross section averaged over the scattering angle of 2° to 15° in the laboratory frame is obtained to be 0.26 µb/sr in the mass region of 1.51-1.55 GeV/c(2). The upper limit of the Θ(+) decay width is obtained to be 0.72 and 3.1 MeV for J(Θ)(P)=1/2(+) and J(Θ)(P)=1/2(-), respectively, using the effective Lagrangian approach.

Three-body nonmesonic weak decay of the (Lambda)12C hypernucleus.

We have measured the branching ratio of the three-body process in the nonmesonic weak decay of Lambda12C to be 0.29+/-0.13. This result was obtained by reproducing the nucleon and the nucleon pair yields introducing a measured final state interaction. At the same time, we have determined the absolute decay widths, Gamma(n) and Gamma(p), along with Gamma2N, whose relative ratio has been a long-standing puzzle. Including the three-body process, we have successfully reproduced the nucleon energy distribution, the coincidence two-nucleon angular correlation, and the momentum sum distribution simultaneously.

Adrenomedullin inhibits connective tissue growth factor expression, extracellular signal-regulated kinase activation and renal fibrosis.

Systemic administration of the potent vasodilating peptide adrenomedullin reduces cardiac and renal fibrosis in hypertensive animals. Here, we investigated the effects of kidney-specific adrenomedullin gene delivery in normotensive rats after unilateral ureteral obstruction, an established model of renal tubulointerstitial fibrosis. Overexpression of exogenous adrenomedullin in the renal interstitium following ureteral obstruction significantly prevented fibrosis and proliferation of tubular and interstitial cells. In this model, there is upregulation of connective tissue growth factor (CTGF) mRNA expression and extracellular signal-regulated kinase (ERK) phosphorylation, and adrenomedullin overexpression suppressed both of these activities without altering the blood pressure. In NRK-49F renal fibroblasts, adrenomedullin reduced transforming growth factor-beta-induced CTGF and fibronectin mRNA upregulation through the cyclic AMP/protein kinase A signaling pathway, and suppressed ERK phosphorylation and cell proliferation. In the kidneys with an obstructed ureter, adrenomedullin receptor gene expression was upregulated along with cyclic AMP production in kidney slices. The latter effect was partially blocked by a neutralizing antibody to adrenomedullin, indicating that an endogenous peptide-receptor system was activated. Our results show that overexpression of exogenous adrenomedullin in the ureteral-obstructed kidney prevents tubulointerstitial fibrosis and cell proliferation through the cyclic AMP-mediated decrease of CTGF induction and ERK phosphorylation.

Role of connective tissue growth factor in profibrotic action of transforming growth factor-beta: a potential target for preventing renal fibrosis.

Tubulointerstitial fibrosis is a crucial process determining the progression and prognosis of various renal diseases. Connective tissue growth factor (CTGF), a novel fibrogenic protein induced by transforming growth factor-beta (TGF-beta), is upregulated in various clinical and experimental nephropathies, but the significance of CTGF in the profibrotic action of TGF-beta is still poorly defined. To explore the implication of CTGF in renal fibrosis, we investigated gene expression of CTGF, fibronectin, and alpha1(I) collagen in an obstructive nephropathy model in rats. Furthermore, to elucidate the role of CTGF in TGF-beta-stimulated extracellular matrix accumulation, we analyzed the effects of blockade of endogenous CTGF using antisense oligodeoxynucleotides (ODNs) in cultured rat renal fibroblasts. After unilateral ureteral obstruction, TGF-beta1 and CTGF messenger RNA (mRNA) expression in the obstructed kidney was coordinately upregulated from the early stage of interstitial fibrosis, followed by marked induction of fibronectin and alpha1(I) collagen mRNA expression. In cultured normal rat kidney fibroblast (NRK-49F) cells, CTGF antisense ODN transfection significantly attenuated TGF-beta1-induced fibronectin and alpha1(I) collagen mRNA expression compared with control reverse ODNs. These results indicate that CTGF has a crucial role in the profibrotic action of TGF-beta in renal fibroblasts, providing a potential therapeutic target against tubulointerstitial fibrosis.

Asymmetry in the nonmesonic weak decay of polarized (5)(Lambda)He hypernuclei

We have measured the asymmetric emission of protons from the nonmesonic decay of polarized (5)(Lambda)He produced by the (pi(+), K+) reaction. (5)(Lambda)He is an s-shell hypernucleus and its polarization is due to the Lambda. One expects to obtain direct information on the elementary weak Lambda-->p-->np process. The asymmetry parameter has been determined to be 0.24+/-0.22. The implication of the result is discussed.

Immunohistological analysis of P53 expression in human skin tumors.

The p53 expression in various skin tumors was immunohistologically evaluated using two mouse monoclonal anti-p53 antibodies, PAb421 and PAb1801. The p53 expression was not detected in the normal epidermal cells. Nuclear staining suggested that the p53 expression was observed in 10 of 26 squamous cell carcinomas (SCCs) from 24 patients, in one undifferentiated carcinoma, one proliferating trichilemmal cyst, one malignant proliferating trichilemmal tumor and in one metastatic carcinoma of breast cancer. None off four cases of Bowen's disease (SCC in situ) showed nuclear staining. In the SCCs, five of 20 primary lesions, three of four recurrent lesions and both of two metastatic lesions had positive nuclei. There was one case of SCC in which a primary lesion was negative but a recurrent lesion was positive. Thus, p53 expression was more frequently observed in SCCs at more clinically advanced stages. This may suggest that p53 has some relevance to progression of SCC. Nuclear staining was not detected in any of the following cases: two cases of seborrheic keratosis, one eccrine poroma, one keratoacanthoma, 11 basal cell epitheliomas, two mammary Paget's disease, three genital Paget's disease, one sebaceous carcinoma, four malignant melanomas, six lymphomas, two leukemia cutis and two angiosarcomas.

Sensing of cadmium and copper ions by externally exposed ADL, ASE, and ASH neurons elicits avoidance response in Caenorhabditis elegans.

We developed a quantitative assay for Caenorhabditis elegans avoidance behavior. This was then used to demonstrate that the worm moved away from toxic concentrations of Cd2+ and Cu2+, but not Ni2+, all ions that prevented development from larval to adult stages. Mutants that have structural defects in ciliated neurons (che-2 and osm-3) as well as worms with three laser-operated neurons (ADL, ASE, and ASH), showed no avoidance behavior from Cd2+ and Cu2+. These results suggest that the avoidance from Cd2+ and Cu2+ are mediated through multiple neural pathways including ADL, ASE, and ASH neurons. We hypothesize that the three sensing neurons provide increased accuracy of the sensory response and a survival advantage in the natural environment of the worm.

Role of adrenomedullin and its receptor system in renal pathophysiology.

Adrenomedullin (AM), a potent vasorelaxing, natriuretic and cell growth-modulating peptide, is thought to act as an autocrine/paracrine regulator in renal glomeruli and tubules. AM receptors comprise the calcitonin receptor-like receptor (CRLR) and a family of receptor-activity-modifying proteins (RAMPs 1-3); however, the pathophysiological role of AM and its receptor system in the kidney remains to be clarified. We examined the regulation of their expression in a rat model of renal injury and found that RAMP1, RAMP2 and CRLR expressions were markedly upregulated upon induction of fibrosis during obstructive nephropathy. Since AM exerts potent antiproliferative effects in various cell types, upregulation of the AM receptor system may play important roles in modulating the progression of renal diseases.

Acrosome reaction in human spermatozoa.

Human spermatozoa were allowed to undergo the acrosome reaction in vitro by incubation in media with or without reagents known to accelerate the onset of the acrosome reaction. The first observable change before the acrosome reaction was a partial decondensation of the acrosomal matrix. This was followed by invaginations of the outer acrosomal membrane alone or of both the plasma and outer acrosomal membranes, which resulted in formation of many vesicles within the acrosomal cap. Subsequently, the plasma and outer acrosomal membranes fused, but the fusion was seldom seen in the acrosomal cap region. On the other hand, fusion of the two membranes was observed consistently at the anterior end of the equatorial segment of the acrosome. Soon after the membranes over the acrosomal cap disappeared, many vesicles, which were originally within the cap, were seen on or in the vicinity of the inner acrosomal membrane. These vesicles dispersed eventually, leaving the inner acrosomal membrane completely exposed. Thus the acrosome reaction in human spermatozoa seems to proceed in a way somewhat different from that in spermatozoa of most other species, although the end result of the reaction is the same.

Cytotoxic triterpenes from Cleome africana.

Eighteen dammarane-type triterpenes were obtained from the whole plant of Cleome africana by means of cytotoxic bioassay-directed fractionation. Twelve of them were novel compounds whose structures were elucidated by various spectroscopic methods.

Granulomatous lobular mastitis: difficulty of diagnosis.

We report a case of a rare inflammatory disease, granulomatous lobular mastitis. Two weeks prior to admission the patient, a 43 year-old woman, (gravida 1, para 1) had noticed a left breast mass associated with tenderness. Palpation, gross inspection, and clinical examination, as well as the rapid growth of the mass lesion led us to believe that it was highly suspicious of malignant neoplasm. Mammography, ultrasonography, and computed tomography did not differentiate it from a malignant neoplasm. Aspiration cytology revealed an inflammatory lesion with a few clusters of epithelial cells it was diagnosed as borderline malignancy(class III) by a prudent pathologist, and thus mastectomy was performed. However, the final histologi-cal diagnosis was granulomatous lobular mastitis with no evidence of malignancy. As the clinical manifestations of granulomatous mastitis are similar to those of mammary carcinoma and, as it is an inflammatory lesion of uncertain etiology and pathogenesis, it has often been mistaken clinically for carcinoma and treated as such. Our review of the literature indicated that granulomatous mastitis most often occurs in young patients with a history of childbirth or oral contraceptive usage. Recurrence was documented in 38% of patients, and, accordingly long-term follow-up by aspiration cytology, complete resection, and adequate drug treatment with corticosteroids are recommended.

Enhanced neointima formation and attachment on the high-porosity inner surface of modified PTFE vascular grafts.

Highly porous PTFE arterial prostheses form endothelium more extensively than the low-porosity grafts in clinical use, but are subject to seroma formation. PTFE vascular grafts were modified to produce a highly porous inner layer (inner layer 60 or 90 microns, outer layer 20 microns). The effect of this modified, composite design on the histology of graft healing was investigated. Twenty-five modified and 25 control grafts, each 4 mm in diameter by 5 cm in length, were implanted into carotid and femoral arteries of dogs. No late seroma formation was observed. After 12 and 18 weeks, the neointima of the grafts was examined by light microscopy and scanning electron microscopy. At 2- and 4-mm distances from the proximal and distal anastomoses, intimal thickness of the control grafts was 238.7 and 96.1 microns, respectively; for the modified grafts it was 236.2 and 202.8 microns at 18 weeks. Thus, the neotinima of modified grafts was thicker than that of control grafts when measured at 4 mm from the anastomoses. Neointimal coverage was less extensive in the control grafts than in modified grafts (26.8 +/- 6.1% vs. 58.8 +/- 13.2%; p < .05). Smooth muscle cells were seen on light-microscopy to penetrate the highly porous inner layer; on scanning electron microscopy, the PTFE fibrils appeared to anchor the neointima of the modified graft. The results suggest that modified PTFE grafts with an inner surface of 60 or 90 microns internodal distance have enhanced formation and anchoring of neointima while remaining impervious to blood.

High porosity PTFE improves endothelialization of arterial grafts without increasing early thrombogenicity.

OBJECTIVE: High porosity (HP) (90 micron internodal distance) PTFE grafts were implanted into the carotid and femoral arteries of dogs to investigate early thrombogenicity, patency, and endothelialization. EXPERIMENTAL DESIGN: Standard PTFE (STD) grafts (30 micron internodal distance) were used as controls. 12 HP and 12 STD grafts were implanted into 6 dogs. Indium-111 labeled platelets were infused intravenously after graft implantation. A graft platelet accumulation index (GPAI) was calculated as the ratio of radioactive emission from the PTFE grafts excised at 48 hours to the emission from a native arterial segment. Another 12 HP and 12 STD grafts were implanted into femoral and carotid arteries to assess patency and endothelialization at 4 and 18 weeks. RESULTS: There was no significant difference in the GPAI of the HP and STD grafts at either the carotid (HP = 31.5 +/- 9.7, STD = 30.6 +/- 11.8; p > 0.05) or femoral (HP = 34.0 +/- 5.0, STD = 31.5 +/- 7.9; p > 0.05) positions. Combined data (carotid and femoral HP vs. carotid and femoral STD) also did not demonstrate a difference in GPAI (HP = 32.8 +/- 7.5, STD = 31.1 +/- 9.6; p > 0.05). Patency rates were the same at 4 weeks (75%), but greater in the HP grafts at 18 weeks (HP = 75%, STD = 37%; p > 0.05). No difference was noted in the percentage of graft endothelialization at 4 weeks (HP = 5.2 +/- 5.8, STD = 5.0 +/- 4.0; p > 0.05), however, at 18 weeks the HP graft had significantly more endothelial coverage compared to STD grafts (HP = 75.2 +/- 13.9, STD = 22.6 +/- 9.5; p < 0.01). CONCLUSIONS: Given that HP PTFE is no more thrombogenic than STD PTFE, and that it provides superior endothelialization, HP grafts should continue to be developed and studied for potential clinical use.

Selective targeting and photodynamic destruction of intimal hyperplasia by scavenger-receptor mediated protein-chlorin e6 conjugates.

BACKGROUND: Photosensitizers, such as Photofrin II or Chloroaluminum-sulfonated phthalocyanine accumulate at sites of arterial injury. We have exploited this property to develop a model of photodynamic therapy (PDT) for intimal hyperplasia. The fluorescent probe [maleylated-bovine serum albumin (mal-BSA) conjugated with Texas-red] can be selectively targeted to intimal macrophages and smooth muscle cells recruited during formation of hyperplasia via a receptor-mediated mechanism. METHODS: In this study, the photosensitizer chlorin e6 (Cle6) was conjugated to mal-BSA in a rat model of intimal hyperplasia, then tested the efficacy of the ligand conjugation to photosensitizer (mal-BSA/Cle6) in PDT of intimal hyperplasia. Arterial wall injury was produced by a balloon catheter pulled through the abdominal aorta of the rat to create a model of intimal hyperplasia. Fluorescent compounds were injected two weeks after injury. RESULTS: Four hours after injection, the intensity of fluorescence achieved with injection of mal-BSA/Cle6 was higher for intimal hyperplastic lesions as compared to control areas. BSA-Cle6 unconjugated did not demonstrate such delivery. Two weeks after balloon injury, the injured aorta was irradiated externally with an argon pumped dye laser four hours following the photosensitizer injection. We employed two total radiant exposures: 20 J/cm2 and 40 J/cm2. Forty-eight hours after PDT, the arteries were examined histologically. Intimal hyperplastic cells were significantly reduced by PDT in the mal-BSA/Cle6 injected group (40-100%) versus the Cle6 group (0-20%). CONCLUSIONS: Mal-BSA/Cle6 is taken up efficiently by a scavenger pathway, localizes in areas of intimal hyperplasia, and functions as a photosensitizer for PDT.

A case of pyoderma gangrenosum on the stump of an amputated right leg.

We present here a case of pyoderma gangrenosum (PG) on the stump of an amputated leg. The patient was a 69-year-old woman who had both of her legs amputated due to acute arterial occlusion. An ulcer first appeared nine years later, after which point it continued to fluctuate in size. Complications included regional blood flow disorder at the amputated stump, diabetes, and secondary infection. Despite various therapies, the ulcer exacerbated, and hypoproteinemia, increased CRP, and fever were confirmed. The patient was diagnosed as having PG based on her clinical symptoms and because the ulcer did not respond to various therapies. The ulcer improved significantly in response to administration of 40 mg/day of prednisolone, and complete epithelialization was later achieved. Given the presence of multiple complications, it was extremely difficult to confirm PG. Therefore, it is important for physicians to consider PG as one of the causes of intractable ulcers.