Precise Measurement of Differential Cross Sections of the Σ

The differential cross sections of the Σ^{-}p→Λn reaction were measured accurately for the Σ^{-} momentum (p_{Σ}) ranging from 470 to 650 MeV/c at the J-PARC Hadron Experimental Facility. Precise angular information about the Σ^{-}p→Λn reaction was obtained for the first time by detecting approximately 100 reaction events at each angular step of Δcosθ=0.1. The obtained differential cross sections show a slightly forward-peaking structure in the measured momentum regions. The cross sections integrated for -0.7≤cosθ≤1.0 were obtained as 22.5±0.68 [statistical error(stat.)] ±0.65 [systematic error(syst.)] mb and 15.8±0.83(stat)±0.52(syst) mb for 470

Observation of Coulomb-Assisted Nuclear Bound State of Ξ

In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.

Addiction to the IGF2-ID1-IGF2 circuit for maintenance of the breast cancer stem-like cells.

The transcription factor nuclear factor-κB (NF-κB) has important roles for tumorigenesis, but how it regulates cancer stem cells (CSCs) remains largely unclear. We identified insulin-like growth factor 2 (IGF2) is a key target of NF-κB activated by HER2/HER3 signaling to form tumor spheres in breast cancer cells. The IGF2 receptor, IGF1 R, was expressed at high levels in CSC-enriched populations in primary breast cancer cells. Moreover, IGF2-PI3K (IGF2-phosphatidyl inositol 3 kinase) signaling induced expression of a stemness transcription factor, inhibitor of DNA-binding 1 (ID1), and IGF2 itself. ID1 knockdown greatly reduced IGF2 expression, and tumor sphere formation. Finally, treatment with anti-IGF1/2 antibodies blocked tumorigenesis derived from the IGF1Rhigh CSC-enriched population in a patient-derived xenograft model. Thus, NF-κB may trigger IGF2-ID1-IGF2-positive feedback circuits that allow cancer stem-like cells to appear. Then, they may become addicted to the circuits. As the circuits are the Achilles' heels of CSCs, it will be critical to break them for eradication of CSCs.

Immunohistochemical prognostic indicators of gastrointestinal carcinoid tumours.

AIMS: The aim of this study was to determine whether expression of the oncoproteins p21, p53, E-cadherin (EC), cyclin D1, bcl-2 and Rb and the proliferation marker Ki-67 is predictive of malignant behaviour in gastrointestinal carcinoid tumours. METHODS: Immunohistochemical (IHC) staining was performed on carcinoid tumours from 41 patients (31 rectal, eight gastrointestinal, two appendiceal lesions). The six tumours that had invaded deeply into the muscularis propria or beyond, had metastasized to regional lymph nodes or had metastasized to a distant site were classified as the malignant group, and the other 35 tumours formed the benign group. IHC expression was compared between the two groups, and the prognostic value of each marker was assessed. RESULTS: Of the six tumours in the malignant group, 66.7% were p21 positive, 0% were p53 positive, 33.3% were EC positive, 100% were cyclin D1 positive, 33.3% were Rb positive, 16.7% were bcl-2 positive and 50% were Ki-67 positive. Of the 35 tumours in the benign group, 17.1% were p21 positive, 0% were p53 positive, 100% were EC positive, 94.3% were cyclin D1 positive, 8.6% were Rb positive, 17.1% were bcl-2 positive and 0% were Ki-67 positive. CONCLUSIONS: These data show that p53, cyclin D1, Rb, bcl-2 and Ki-67 staining does not correlate with malignant behaviour but that overexpression of p21 (P=0.02) and reduced staining of EC (P=0.005) do correlate with malignant behaviour. These two parameters may therefore be useful as prognostic indicators for gastrointestinal carcinoid tumours.

Ischaemic preconditioning ameliorates functional disturbance and impaired renal perfusion in rat ischaemia-reperfused kidneys.

1. The effects of ischaemic preconditioning (IP) on renal function, haemodynamics and lipid peroxidation in the rat ischaemia-reperfused kidney model were examined. 2. In Wistar male rats, application of a single or three periods of 5 min bilateral renal ischaemia was performed prior to 30 min bilateral ischaemia and 90 min reperfusion (IR). The glomerular filtration rate (GFR) was estimated in terms of inulin clearance. Fractional excretion of sodium (FE(Na)) and lithium (FE(Li)), indicating total and proximal tubular sodium handling, respectively, was also measured and renal blood flow was monitored throughout the experiment. In addition, renal lipid peroxidation (LPO) levels in reperfused kidneys were evaluated. 3. A 2.8-fold increase in recovery of GFR (P < 0.005), a 50% reduction in FE(Na) (P < 0.005) and a 40% decrease in FE(Li) (P < 0.05) after IR resulted from the single period of 5 min IP. Renal blood flow was also higher than that in the control group (P < 0.01). No change of LPO levels was observed. 4. We conclude that IP may have an ability to ameliorate reperfused renal function and haemodynamics with a suitable period of preconditioned ischaemia, although this effect is independent of LPO.

Telomerase activity and telomere length in benign and malignant human thyroid tissues.

Several studies have demonstrated that telomerase is activated and telomere length is altered in various types of tumors. In this study, we investigated telomerase activities and telomere length in 21 thyroid tumors. Telomerase activity was detected in 11 of 12 thyroid cancers and three of nine follicular adenomas. The mean telomere lengths in the cancers tissue and follicular adenomas were lower than in the respective background tissues, the differences being significant (P=0.0055 and P<0.006), respectively. Our findings suggest that change in telomerase activity and telomere length may be important for development of thyroid tumors.

Review of 41 patients operated on for primary hyperparathyroidism.

We reviewed 41 cases of operation for primary hyperparathyroidism (PHPT) in our institution between 1987 and 1999. The objective of this study was 1) to evaluate the sensitivity and positive predictive value of several localization studies for an enlarged parathyroid gland; 2) to determine whether a selective. unilateral-exploration operation is safe; and 3) to investigate rates of coexisting malignancies of other organs. A total of 61 enlarged parathyroid glands (701 +/- 131 mg wt) were removed, and the lesions consisted of 32 adenomas, two cancers, and seven hyperplasias. MIBI scintigraphy had both a high sensitivity (88.9%) and positive predictive value (88.9%) for localization of abnormal parathyroid glands and yielded better performance than the other techniques, including ultrasonography, CT scanning, and Tl-Tc scintigraphy. However, all of the localization techniques failed to detect enlarged glands (18/32 glands = 62.5%) in patients with multi-glandular parathyroid lesions. Initial operations with selective unilateral exploration of the neck were successful in 23 of 24 patients (95.8%). Operative failure was due to missing the second adenoma of a double adenoma. Malignant tumors were found in 11 patients (26.8%) previously treated or concurrently managed at the time of parathyroidectomy. There was a significant increase in serum-intact PTH level in patients with concurrent malignant tumors compared to patients who had no association of malignancies. In conclusion, 1) at least two preoperative localization tests, an MIBI scan and ultrasonography, are helpful in accurately localizing an abnormal parathyroid gland; 2) selective unilateral exploration is safe and desirable if the second ipsilateral gland is normal macroscopically; and 3) systematic examination for malignant tumors is necessary in PHPT patients before and after parathyroidectomy.

Catecholamine and cytokine response to laparoscopic adrenalectomy in patients with pheochromocytoma.

This study assesses the surgical stress of laparoscopic adrenalectomy (LA) in patients with pheochromocytoma using catecholamine and cytokine. The study was conducted on one patient who had laparoscopic adrenalectomy performed for pheochromocytoma, and three patients as controls who had undergone laparoscopic cholecystectomy (LC) for cholecystolithiasis. Catecholamines, tumor necrosis factor alpha (TNFalpha) and interleukin 6 (IL-6) were measured at 30-minute intervals intraoperatively, and on the first, third and fifth postoperative days (POD) respectively. Plasma TNFalpha and IL-6 were measured by a commercially available sandwich enzyme-linked immunosorbent assay test. During the operation. changes of catecholamine concentration in LA were far larger than those in LC. The changes of TNFalpha concentration in LA were also larger than those in LC. TNFalpha returned to basal value at the end of the operation in LC, but it did not in LA. TNFalpha concentration in LC changed a little after the surgery, whereas that in LA sharply increased and was maintained at a high level from 1 POD until 5 POD. Enhanced cytokine responses were observed in LA compared to LC during and after the surgery. We concluded that laparoscopic adrenalectomy may give those patients with pheochromocytoma more surgical stress than laparoscopic cholecystectomy for cholecystolithiasis, during and after the operation.

Inhibitory effect of aldosterone on the natriuretic response to atrial natriuretic peptide in hypocapnic rats.

UNLABELLED: 1. Previous studies have shown that acute hypocapnia blunts the natriuretic effect of atrial natriuretic peptide (ANP) independently of the renal nerves and that the effect of ANP is restored by total adrenalectomy. We investigated the natriuretic response to ANP in potassium canrenoate (aldosterone receptor antagonist)-treated rats to clarify whether aldosterone contributes to the attenuated natriuretic response to ANP during hypocapnia. 2. Wistar rats, challenged with either canrenoate or saline vehicle, were infused with 10 micrograms/kg per h ANP during acute hypocapnia achieved by mechanical ventilation. 3. In saline-treated hypocapnic rats, ANP infusion failed to increase the fractional excretion of sodium (FENa) (from 3.49 +/- 0.26 to 5.03 +/- 0.42%, respectively; n = 6) which was similar to values for time control rats (from 3.00 +/- 0.61 to 4.41 +/- 0.68%; n = 6). The hyporesponsiveness to ANP during hypocapnia was also evident when the FENa was compared with that of normocapnic rats (from 3.92 +/- 0.69 to 7.87 +/- 0.45%; P < 0.05; n = 6). In canrenoate-treated rats, ANP infusion caused greater increases in sodium excretion (FENA from 3.05 +/- 0.71 to 7.21 +/- 0.45%; P < 0.05; n = 8) than saline infusion (FENA from 4.16 +/- 1.11 to 5.47 +/- 0.66%; n = 6), despite the hypocapnia. The increase in FENA after ANP infusion during hypocapnia (4.16 +/- 0.86%) was similar to the increase seen during normocapnia (3.89 +/- 0.86%; n = 9). 4. IN CONCLUSION: (i) acute hypocapnia blunts the natriuretic effects of ANP; and (ii) this attenuation is restored by potassium canrenoate treatment. The data suggest that aldosterone plays an important role by limiting the renal actions of ANP during acute hypocapnia.

Inappropriate elevation of intact PTH in the presence of normocalcemia after successful surgery for primary hyperparathyroidism.

We describe here a patient with primary hyperparathyroidism who had high serum intact PTH levels for over 16 months after parathyroidectomy without signs of recurrence or persistence of the disease. The patient was a 48-year-old female who appeared well nourished (body mass index, 23.7). She was received subtotal gastrectomy as treatment for a duodenal ulcer at 44 years and 5 months old and had reached menopaused at 46 years of age. Hypercalcemia and a high serum intact PTH level were pointed out three months before admission to our institute. A bone densitometric study revealed that the bone mass of the lumbar spine was extremely reduced (0.636 g/cm2, Z score, -2.17) preoperatively and had not increased 29.5 months after parathyroidal adenomectomy (0.656 g/cm2, Z score, -1.97). Hyperparathyroidism, menopause and gastrectomy may have together contributed to the reduced bone mass. The postoperative persistently increased PTH levels in our patient suggest that the remaining parathyroid glands could have been altered during hypercalcemia, causing an increase in the set-point of PTH secretion by serum calcium or a decrease in the renal responsiveness to PTH during the disease.

Adrenalectomy overcomes the blunted natriuretic response to atrial natriuretic peptide during hypocapnia in rats.

1. Hypocapnia has been shown to blunt the natriuretic effect of atrial natriuretic peptide (ANP) independently of the renal nerves. In order to examine whether the adrenal glands are a limiting factor for the natriuretic effect of ANP, we evaluated the natriuretic responses of adrenalectomized rats to ANP infusion during hypocapnia. 2. Rats subjected to total adrenalectomy (ADX) or sham-operation (sham) were divided into hypocapnic and normocapnic groups depending on their arterial PCO2 levels. 3. In sham rats, ANP infusion at a rate of 12 micrograms/kg per h resulted in a smaller increase in the fractional excretion of sodium during hypocapnia (mean +/- SEM: 1.02 +/- 0.40%, n = 10) than normocapnia (3.95 +/- 0.64%, n = 9; P < 0.001). The level of fractional excretion of sodium with ANP infusion during hypocapnia was not significantly different from the level in saline-infused hypocapnic sham rats (0.93 +/- 0.62%, n = 10). In hypocapnic ADX rats (n = 11), ANP induced greater increases in the fractional excretion of sodium (5.59 +/- 1.35%) than did saline infusion (1.04 +/- 1.02%, n = 10; P < 0.002). In the absence of adrenal glands, the magnitude of natriuresis after ANP infusion during hypocapnia and normocapnia (3.32 +/- 1.07%, n = 9) were the same. 4. We conclude that the natriuretic effect of ANP is blunted during hypocapnia in the presence, but not in the absence, of adrenal glands. Our data suggest that the adrenal glands have an important role in limiting the natriuretic effect of ANP.

Effect of glutamine on acute lung injury in rats with endotoxemia.

We administered endotoxin to rats to produce an acute lung injury model, and assessed the effect on respiratory function when glutamine was added to the solution for total parenteral nutrition. Rats given total parenteral nutrition with glutamine as 33% of the amino acid content were compared with rats given no glutamine. Endotoxin (500 microg/kg) was administered intravenously after 72 h of total parenteral nutrition. The survival rate and the nitrogen balance were significantly improved (P < 0.05) at 48 h after endotoxin administration as a result of glutamine treatment. In addition, the arterial oxygen partial pressure was significantly increased (P < 0.01) and the wet: dry lung weight ratio was decreased (P < 0.05) by glutamine. These results suggested that glutamine improved endotoxin-induced acute lung injury in rats.

Spontaneous autoimmune skin lesions of MRL/n mice: autoimmune disease-prone genetic background in relation to Fas-defect MRL/1pr mice.

The autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mouse is characterized by the lpr mutation, which is a defect in the Fas antigen. Since Fas mediates apoptosis, this defect results in CD4-CD8- double negative T-cell proliferation, lupus nephritis, and macroscopic lupus erythematosus-like skin lesions. The control counterpart of MRL/lpr mouse is the MRL/Mp-+/+ (MRL/n) mouse, which lacks the lpr mutation and is almost normal during the first 6 mo of life. The lpr mutation, however, accelerates autoimmune phenomena in MRL/lpr mice. Thus, it is important to investigate autoimmune diseases like systemic lupus erythematosis in relation to the autoimmune disease-prone genetic background of MRL/n mice. We found that skin lesions in aged MRL/n mice had unique characteristics. The first characteristic is spontaneous occurrence, and the second is epidermal cell nuclear immunostaining with IgGs by direct immunofluorescence. The skin lesions in aged MRL/n mice showed milder inflammation than in MRL/lpr mice. A homogeneous pattern of epidermal cell nuclear staining was always associated with nuclear staining in kidney cells and also correlated with the in vitro binding of sera to keratinocytes cultured from newborn MRL/n mice. These results suggest that the skin lesions of aged MRL/n mice are a good model for certain types of cutaneous lupus erythematosus and also can provide new insights into the long-standing controversy whether epidermal cell nuclear staining occurs in vivo.

Resistance to natriuresis in patients with peritonitis carcinomatosa.

The natriuretic effect of atrial natriuretic peptide (ANP) is blunted in certain clinical disorders such as congestive heart failure and liver cirrhosis, despite the elevated plasma ANP levels. These sodium-retaining states are characterized by increased activity of the renal sympathetic nerves. Recent studies have shown higher levels of circulating and urinary catecholamines in cancer patients. We hypothesized that the increased adrenergic activity may be responsible for ascites formation in patients with peritonitis carcinomatosa (PC). The objective of this study was to determine the renal responses to endogenous ANP in patients with PC. Patients, hospitalized at our institute for PC, were examined using renal clearance studies for 2 h. Non-cancer patients were also examined as control subjects. Statistical analysis was performed using Wilcoxon's rank sum test. The results showed that absolute and fractional sodium excretions were markedly lower in patients with PC (54 +/- 16 microEq/min, means +/- SE, p < 0.0005; 0.55 +/- 0.15%, p < 0.005) than in control patients (166 +/- 14 microEql/min; 1.14 +/- 0.09%, respectively). Plasma ANP concentration was increased in patients with PC (34.7 +/- 8.4 pg/ml, p < 0.001) in comparison with control patients (13.3 +/- 2.0 pg/ml). Plasma and urinary levels of norepinephrine were significantly higher in cancer patients (0.36 +/- 0.10 ng/ml, p < 0.05; 125 +/- 20 ng/dl GF, p < 0.05) than in the controls (0.17 +/- 0.02 ng/ml; 73 +/- 13 ng/dl GF). These results suggest that increased renal sympathetic nerve activity may contribute to the attenuation of the natriuretic effect of ANP in patients with PC.

Coexistence of pemphigus and bullous pemphigoid.

Widespread tense blisters developed on a 60-year-old Japanese man who had been diagnosed with pemphigus 11 years earlier, because of a history of pruritic erythema and erosions on his face, chest, and back, mild supra-basal layer blister formation found in a biopsy specimen, and a positive direct immunofluorescence test showing IgG deposition in the intercellular space. The histological findings showed subepidermal blister, and the immunoblot study detected 180kD bullous pemphigoid antigen. Direct immunofluorescence test revealed intercellular staining for IgG, and indirect immunofluorescence tests repeatedly demonstrated the presence of circulating antibodies to the intercellular space. From these observations, this case suggests the coexistence of pemphigus and bullous pemphigoid.

Evaluation of the Japanese-Chinese herbal medicine, kampo, for the treatment of lupus dermatoses in autoimmune prone MRL/Mp-lpr/lpr mice.

Kampo, a Japanese-Chinese traditional herbal medicine, has been used for the treatment of various diseases for about 3,000 years in China. Among herbal medicines, Sairei-to is well known for improving the symptoms of rheumatoid arthritis (RA) and other collagen diseases. However, its immunosuppressive effects on autoimmune cutaneous phenomena are not completely understood. We investigated the effects of Sairei-to on the development of lupus dermatoses in autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mice, an animal model which spontaneously develops skin lesions similar to those seen in human lupus erythematosus. Virgin female MRL/lpr mice at 1 month of age, which were treated orally with Sairei-to, had reduced amounts of IgG deposition at the dermoepidermal junction, titers of anti-DNA antibodies and rheumatoid factor, and lymphoproliferation. These results support the use of traditional herbal medicines in patients with human RA and systemic lupus erythematosus.

Giant metastatic malignant melanoma with an unknown primary site.

We report a case of malignant melanoma of unknown primary origin which presented with a giant metastatic tumor in his right inguinal region. A 94-year-old man noticed a small subcutaneous tumor in the right inguinal region 3 years earlier, which eventually became as larger as 9 cm in diameter without treatment. Although a histological examination of the lesion showed malignant melanoma, extensive examination did not reveal its primary lesion or any metastasis other than that to the right inguinal area. Our case took an interesting course in that this well-growing metastatic tumor was localized in only one region and supported a previous report indicating that malignant melanoma with unknown primary origin has a low tendency to metastasize and a relatively good prognosis.

Susceptibility to UVB light in cultured keratinocytes of cutaneous lupus erythematosus.

In this study, we investigated UVB-light-induced cytotoxicity and the binding of antibodies to extractable nuclear antigens on cultured keratinocytes from patients with cutaneous lupus erythematosus (LE). Keratinocytes from cutaneous LE patients showed a higher susceptibility to single-dose UVB light irradiation compared to keratinocytes from normal controls. The binding of antibodies to U1RNP and Ro/SS-A antigens on cultured keratinocytes was induced by UVB light and more up-regulated when cultured keratinocytes were reacted with autologous sera. Antibody-dependent cellular cytotoxicity (ADCC) was induced when cultured keratinocytes irradiated with UVB light were combined with autologous sera, using peripheral mononuclear cells of normal controls. Immunohistochemical studies of skin biopsy specimens from patients with systemic LE revealed an increased number of epidermal Langerhans cells at the peripheral sites of skin lesions and a relative dominance of infiltrative CD8-positive lymphocytes in the central area of skin lesions. Based on these findings we suggested that ADCC mechanisms were involved in the development of skin lesions, and the distribution of Langerhans cells and infiltrated CD8 cells were responsible for the expansion and persistence of lesions.