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Understanding how super-massive black holes form and grow in the early Universe has become a major challenge1,2 since it was discovered that luminous quasars existed only 700 million years after the Big Bang3,4. Simulations indicate an evolutionary sequence of dust-reddened quasars emerging from heavily dust-obscured starbursts that then transition to unobscured luminous quasars by expelling gas and dust5. Although the last phase has been identified out to a redshift of 7.6 (ref. 6), a transitioning quasar has not been found at similar redshifts owing to their faintness at optical and near-infrared wavelengths. Here we report observations of an ultraviolet compact object, GNz7q, associated with a dust-enshrouded starburst at a redshift of 7.1899 ± 0.0005. The host galaxy is more luminous in dust emission than any other known object at this epoch, forming 1,600 solar masses of stars per year within a central radius of 480 parsec. A red point source in the far-ultraviolet is identified in deep, high-resolution imaging and slitless spectroscopy. GNz7q is extremely faint in X-rays, which indicates the emergence of a uniquely ultraviolet compact star-forming region or a Compton-thick super-Eddington black-hole accretion disk at the dusty starburst core. In the latter case, the observed properties are consistent with predictions from cosmological simulations7 and suggest that GNz7q is an antecedent to unobscured luminous quasars at later epochs.An unusual ultraviolet compact object associated with a dusty starburst has been observed at a redshift of about 7.2, with a luminosity that falls between that of quasars and galaxies, possibly in transition between the two. [ABSTRACT FROM AUTHOR]

Background/Objectives: Depression and hopelessness are frequently experienced in chronic kidney disease (CKD) and are generally associated with lessened physical activity. The aim of this study was to quantify the associations between sarcopenia as determined by SARC-F with both depression and hopelessness. Design and Setting: This multicenter cohort study involving cross-sectional and longitudinal analyses was conducted in a university hospital and four general hospitals, each with a nephrology center, in Japan. Participants: Participants consisted of 314 CKD patients (mean age 67.6), some of whom were receiving dialysis (228, 73%). Measurements: The main exposures were depression, measured using the Center for Epidemiologic Studies Depression (CES-D) questionnaire, and hopelessness, measured using a recently developed 18-item health-related hope scale (HR-Hope). The outcomes were sarcopenia at baseline and one year after, measured using the SARC-F questionnaire. Logistic regression models were applied. Results: The cross-sectional and longitudinal analyses included 314 and 180 patients, respectively. Eighty-nine (28.3%) patients experienced sarcopenia at baseline, and 44 (24.4%) had sarcopenia at the one-year follow-up. More hopelessness (per 10-point lower, adjusted odds ratio [AOR]: 1.33, 95% confidence interval [95% CI] 1.12–1.58), depression (AOR: 1.87, 95% CI 1.003–3.49), age (per 10-year higher, AOR: 1.70, 95% CI 1.29–2.25), being female (AOR: 2.67, 95% CI 1.43–4.98), and undergoing hemodialysis (AOR, 2.92; 95% CI, 1.41–6.05) were associated with a higher likelihood of having baseline sarcopenia. More hopelessness (per 10-point lower, AOR: 1.69, 95% CI 1.14–2.51) and depression (AOR: 4.64, 95% CI: 1.33–16.2) were associated with a higher likelihood of having sarcopenia after one year. Conclusions: Among patients with different stages of CKD, both hopelessness and depression predicted sarcopenia. Provision of antidepressant therapies or goal-oriented educational programs to alleviate depression or hopelessness can be useful options to prevent sarcopenia. [ABSTRACT FROM AUTHOR]

The wake flow originated by three-dimensional bluff bodies having the different aspect ratio is experimentally studied in this paper. The turbulent wakes generated by asymmetric- and semi-cylinders were first measured by the high-speed PIV. The time-averaged and instantaneous flow structures were analyzed in various planes. Then, the orthogonal wavelet multi-resolution technique was used to analyze the multi-scale flow structures. The instantaneous vorticity and Reynolds shear stresses of various frequencies were evaluated and compared among the different aspect ratio and body shape. It was found that the asymmetric-cylinder produces the aerodynamic downforce and its separation region is smaller than that of semi-cylinder. The large-scale structure makes the most contribution to vorticities, and the intermediate-scale structure dominates the flow structures near the tip of body. The large-scale structure makes the most contribution to Reynolds shear stress except the tip of body, accounting for about 55.9-79.2%. The maximum value of large-scale Reynolds shear stress appears at the end of separation region, and the small-scale Reynolds shear stress exhibits the maximum value in the shear layer of the body surface. Graphical Abstract: [ABSTRACT FROM AUTHOR]

The superconducting fluctuation effect, due to preformed Cooper pairs above the critical temperature Tc, has been generally understood by the standard Gaussian fluctuation theories in most superconductors. The transverse thermoelectric (Nernst) effect is particularly sensitive to the fluctuations, and the large Nernst signal found in the pseudogap regime of the underdoped cuprates has raised much debate. Here we report on the observation of a colossal Nernst signal due to the superconducting fluctuations in the heavy-fermion superconductor URu2Si2. The Nernst coefficient is anomalously enhanced (by a factor of ∼106) as compared with the theoretically expected value of the Gaussian fluctuations. Moreover, contrary to the conventional wisdom, the enhancement is more significant with a reduction of the impurity scattering rate. This unconventional Nernst effect intimately reflects the highly unusual superconducting state of URu2Si2. The results invoke possible chiral or Berry-phase fluctuations associated with the broken time-reversal symmetry of the superconducting order parameter. [ABSTRACT FROM AUTHOR]

Metformin, the major target of which is liver, is commonly used to treat type 2 diabetes. Although metformin activates AMP-activated protein kinase (AMPK) in hepatocytes, the mechanism of activation is still not well known. To investigate AMPK activation by metformin in liver, we examined the role of reactive nitrogen species (RNS) in suppression of hepatic gluconeogenesis. To determine RNS, we performed fluorescence examination and immunocytochemical staining in mouse hepatocytes. Since metformin is a mild mitochondrial complex I inhibitor, we compared its effects on suppression of gluconeogenesis, AMPK activation and generation of the RNS peroxynitrite (ONOO−) with those of rotenone, a representative complex I inhibitor. To determine whether endogenous nitric oxide production is required for ONOO− generation and metformin action, we used mice lacking endothelial nitric oxide synthase (eNOS). Metformin and rotenone significantly decreased gluconeogenesis and increased phosphorylation of AMPK in wild-type mouse hepatocytes. However, unlike rotenone, metformin did not increase the AMP/ATP ratio. It did, however, increase ONOO− generation, whereas rotenone did not. Exposure of eNOS-deficient hepatocytes to metformin did not suppress gluconeogenesis, activate AMPK or increase ONOO− generation. Furthermore, metformin lowered fasting blood glucose levels in wild-type diabetic mice, but not in eNOS-deficient diabetic mice. Activation of AMPK by metformin is dependent on ONOO−. For metformin action in liver, intra-hepatocellular eNOS is required. [ABSTRACT FROM AUTHOR]

Na+/K+-ATPase inhibition by ouabain suppresses ATP production by generating reactive oxygen species (ROS) and impairs glucose-induced insulin secretion from pancreatic islets. To clarify the signal-transducing function of Na+/K+-ATPase in decreasing ATP production by the generation of ROS in pancreatic islets, the involvement of Src was examined. In addition, the significance of Src activation in diabetic islets was examined. Isolated islets from Wistar rats and diabetic Goto–Kakizaki (GK) rats (a model for diabetes) were used. ROS was measured by 5-(and 6)-chloromethyl-2′,7′-dichlorofluorescein fluorescence using dispersed islet cells. After lysates were immunoprecipitated by anti-Src antibody, immunoblotting was performed. Ouabain caused a rapid Tyr418 phosphorylation, indicating activation of Src in the presence of high glucose. The specific Src inhibitor 4-amino-5-(4-chlorophenyl)-7-( t-butyl)pyrazolo[3,4- d]pyrimidine (PP2) restored the ouabain-induced decrease in ATP content and the increase in ROS production. Both PP2 and ROS scavenger restored the impaired insulin release and impaired ATP elevation in GK islets, but had no such effect in control islets. PP2 reduced the high glucose-induced increase in ROS generation in GK islet cells but had no effect on that in control islet cells. Moreover, ouabain had no effect on ATP content and ROS production in the presence of high glucose in GK islets. These results indicate that Src plays a role in the signal-transducing function of Na+/K+-ATPase, in which ROS generation decreases ATP production in control islets. Moreover, ROS generated by Src activation plays an important role in impaired glucose-induced insulin secretion in GK islets, in which Src is endogenously activated independently of ouabain. [ABSTRACT FROM AUTHOR]

We have established a new method for allogeneic pancreatic islet (PI) transplantation: relatively low doses of irradiation followed by simultaneous transplantation of PIs and bone marrow cells (BMCs) via the portal vein (PV). In the present study, we have compared this method with intra-bone marrow (IBM)-bone marrow transplantation (BMT), and with a combination of both methods. Streptozotocin (STZ)-induced diabetic-recipient rats, Fischer 344 (F344, RT1Al, RT1Bl), were irradiated 1 day before transplantation. PIs of Brown Norway rats (BN, RT1An, RT1Bn) were transplanted into the liver of the diabetic F344 rats via the PV. BMCs from BN rats were injected into the recipients' bone marrow (IBM), PV or intravenously (IV) or by a simultaneous combination of PV plus IBM (PV+IBM). We compared graft survival among the groups of ‘9 Gy+IBM’(10/10 accepted), ‘9 Gy+PV’(7/10 accepted), ‘9 Gy+IV’(0/7 accepted), ‘9 Gy+PV+IBM’(8/8 accepted), ‘8.5 Gy+IBM’(4/9 accepted), ‘8.5 Gy+PV’(0/7 accepted), ‘8.5 Gy+IV’(0/7 accepted), ‘8.5 Gy+PV+IBM’(9/12 accepted), ‘8 Gy+IBM’(2/10 accepted) and ‘8 Gy+PV+IBM’(2/8 accepted). As we reported previously, PV-BMT is more effective in inducing the acceptance of allogeneic PIs than IV-BMT. However, IBM-BMT requires less pretreatment than PV-BMT. (PV+IBM)-BMT was found to be the most effective in inducing the acceptance of allogeneic PIs. These results suggest that allogeneic PI-transplantation in conjunction with (PV+IBM)-BMT could become a viable strategy.Bone Marrow Transplantation (2006) 38, 657–664. doi:10.1038/sj.bmt.1705500; published online 2 October 2006 [ABSTRACT FROM AUTHOR]

We retrospectively investigated the efficacy and feasibility of individualised chemotherapy based on in vitro drug sensitivity testing (DST) for patients with glioblastoma multiforme. A total of 40 consecutive patients with glioblastoma multiforme (GM) were enrolled into this study between January 1995 and December 2000. The flow cytometric (FCM) detection of apoptosis was used to determine the in vitro sensitivity of tumour cells obtained at surgery to 30 different kinds of anticancer agents. From the results of FCM assay, an in vitro best regimen was prospectively selected. All the patients concurrently received the individualised chemotherapy with the in vitro best regimen and 60 Gy of conventional radiation therapy. Of the 31 assessable patients, eight patients (26%) achieved partial response, and 20 patients (65%) had stable disease. The median survival time was 20.5 months. The individualised chemotherapy based on in vitro DST was associated with favourable survival time for the patients with GM compared with the reported results of conventional therapy regimens. The present result suggests that the currently available anticancer agents could be effective against GM when used in individualised chemotherapy. [ABSTRACT FROM AUTHOR]

We found a significant correlation between lung cancer in smokers and the expression of a human gene, D40, predominantly expressed in testis and cancers. In an attempt to clone a novel human gene, we screened a cDNA library derived from a human B cell line and obtained a cDNA clone that we refer to as D40. A search for public databases for sequence homologies showed that the D40 gene is identical to AF15q14. D40 mRNA is predominantly expressed in normal testis tissue. However, this gene is also expressed in various human tumour cell lines and primary tumours derived from various organs and tissues, such as lung cancer. We examined the relationship between D40 expression and clinico-pathological characteristics of tumours in primary lung cancer. D40 expression did not significantly correlate with either histological type or pathological tumour stage. However, D40 expression was observed more frequently in poorly differentiated tumours than in well or moderately differentiated ones. Furthermore, the incidence of D40 expression was significantly higher in tumours from patients who smoke than in those from non-smokers. D40/AF15q14 is the first gene in the cancer/testis family for which expression is related to the smoking habits of cancer patients. [ABSTRACT FROM AUTHOR]

Background. Many recent studies have found that several angiogenic factors play an important role in primary and metastatic tumor growth. Platelet-derived growth factor (PDGF) is known to induce angiogenesis. In this study, we investigated whether tumor PDGF can reliably predict metastatic potential and survival benefit in patients with breast cancer. Methods. Histoimmunological analysis with two isoforms of PDGF, PDGF-AA and PDGF-BB, was performed on formalin-fixed, paraffin-embedded tissue. This analysis was performed in 83 patients with breast cancer; 30 with hematogenous recurrence, 13 with locoregional recurrence, and 40 surviving without recurrence. Results. Of the 30 patients with hematogenous recurrence, 13 (43.3%) showed PDGF-AA expression [PDGF-AA(+) group] and the remaining 17 (56.7%) showed no expres-sion of tumor PDGF-AA [PDGF-AA(−) group]. In the locoregional recurrence group, 1 patient (7.7%) showed PDGF-AA expression, and 2 of the 40 patients surviving without recurrence (5%) showed PDGF-AA expression in the primary tumor tissue. In contrast, PDGF-BB expression was observed in all 43 patients with recurrence and in 37 of the 40 patients surviving without recurrence. The PDGF-AA(+) and locoregional recurrence groups had almost the same period to recurrence after surgery (25.2 ± 18.5 months and 24.0 ± 11.3 months, respectively), whereas this period in the PDGF-AA(−) group was significantly longer ( P < 0.0489 and P < 0.0400, respectively) than that of these other two groups. The 2-, 5-, and 8-year survival rates for the PDGF-AA(−) group were 70.6%, 47.1%, and 35.3%, respectively, whereas those for the PDGF-AA(+) group were 61.5%, 23.1%, and 15.4%, respectively; those for the locoregional recurrence group were 76.9%, 23.1%, and 7.7%, respectively. The survival rate for the PDGF-AA(−) group tended to be better ( P = 0.0907) than that for the PDGF-AA(+) group, and showed no difference ( P = 0.148) from that of the locoregional recurrence group. Conclusion. The data on PDGF-BB expression indicate that PDGF-BB is largely concerned with primary tumor growth and is not related to hematogenous metastasis. In contrast, PDGF-AA expression seems to be linked with hematogenous metastasis. [ABSTRACT FROM AUTHOR]

The efficacy of histamine H2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) therapies in healing reflux esophagitis was compared in a prospective randomized case-control comparative study. A total of 71 patients with grade A to D esophagitis (Los Angeles classification) were given either famotidine 20 mg twice a day (Fam; n = 35) or omeprazole 20 mg once daily (Ome; n = 36) for 8 weeks. Endoscopy was performed to assess healing in 57 patients. Healed patients were followed-up without H2RA or PPI therapy for 3 months. At the end of follow-up, endoscopy was able to be performed in 33 patients. Healing rates for patients in the Fam and Ome groups were 58.6% (17/OFF and 97.4% (27/28), respectively (P < 0.001), and when limited to grade A to B, healing rates were 60.9% (14/23) and 100% (25/25), respectively (P < 0.001). Concerning Helicobacter pylori infection, healing rates for the Fam and Ome groups in H. pylori (+) patients were 90.0% (9/10) and 90.9% (10/11), respectively (P = 1.00). Remission rates in the Fam and Ome groups were 45.0% (91/2)) and 33.3% (6/18), respectively (P > 0.4). In regard to alcohol drinking, remission rates of daily and social drinkers were 7.7% and 42.4%, respectively (P < 0.03). Thus, PPI should be the drug of choice even for healing lower-grade reflux esophagitis, especially in H. pylori (-) patients. Treatment with H2RA may be an alternative choice in H. pylori (+) patients. After healing, most patients cannot sustain remission without maintenance therapy. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasonography (EUS) was helpful for the diagnosis of rectal cancer associated with ulcerative colitis. The patient was a 38-year-old Japanese man with a 19-year history of relapsing-remitting type ulcerative colitis involving the entire colon. Routine colonoscopy revealed multiple polypoid prominences in the upper portion of the rectum. EUS revealed a hypoechoic mass in the submucosa beneath and around the polypoid lesion on the most oral side. Signet ring cells were found in a biopsy specimen from this lesion. Subtotal colectomy was performed. A depressed lesion was observed around the prominence on the most oral side; histologically, this lesion was poorly differentiated mucinous and signet ring cell carcinoma extending into the subserosa. The polypoid lesion on the most anal side was well differentiated adenocarcinoma, which was limited to the mucosa. Our findings suggest that EUS is helpful for detecting invasive cancer associated with ulcerative colitis. [ABSTRACT FROM AUTHOR]

Background. The overall survival rate and contributory factors were examined in patients undergoing hemodialysis in one dialysis program. The clinical profiles of dialysis patients who suffered from cerebro- and cardiovascular diseases (CCVD) were also studied. Methods. Data were available for 1064 patients who had received hemodialysis treatment for more than 3 months in our program (17 centers) in Miyazaki, Japan, between 1971 and 1994. Results. The respective 3-, 5-, and 10-year actuarial survival rates were 85%, 79%, and 66%. The Cox proportional hazard model identified three variables: age at start of hemodialysis (adjusted relative hazard [RH], 1.05), sex (RH, 1.42 for males), and type of underlying renal disease (RH, 1.00 for chronic glomerulonephritis, 2.80 for diabetes mellitus, 1.59 for nephrosclerosis), as being significantly associated with survival. Patients with CCVD had a high incidence of cerebral hemorrhage (8.7 per 1000 person-years). Patients whose first CCVD episode occurred within 36 months of starting hemodialysis were older, and more frequently had diabetes mellitus or nephrosclerosis and suffered from cerebral infarction. Long-term hemodialysis patients with CCVD more frequently had chronic glomerulonephritis as the underlying disease and had a higher incidence of cerebral hemorrhage. Conclusion. Age, sex, and underlying renal disease were independent factors that contributed to the mortality of the hemodialysis patients. There was a high incidence of CCVD among the hemodialysis patients, but the etiology of CCVD may differ depending on the underlying renal disease. [ABSTRACT FROM AUTHOR]

Background. Our objective was to investigate changes in left ventricular inflow jet width and long axis motion in patients on maintenance hemodialysis by preload reduction due to a single hemodialysis. Methods. We evaluated 20 patients on stable maintenance hemodialysis by Doppler echocardiography. Twenty age-matched controls were also examined. Transmitral flow, left ventricular long axis M-mode (LAM) echocardiography, and two-dimensional color Doppler early diastolic left ventricular inflow jet width (JW) were analyzed before and after a single hemodialysis. Results. Before hemodialysis, compared with controls, JW was reduced in patients (2.1 ± 0.4 vs 2.4 ± 0.3 cm; P < 0.01), and early diastolic excursion of LAM (LAM-E) was also reduced. Peak velocity of the Doppler transmitral early diastolic wave (E) and late diastolic wave (A) were both higher, while the E/A ratio was lower. After hemodialysis, compared with the predialysis findings, JW and early diastolic excursion of LAM were unchanged; however, Doppler transmitral flow showed decreased E and E/A. Thus, in hemodialysis patients, inflow jet width was narrow, and unchanged by a single hemodialysis, while the Doppler transmitral flow pattern was changed mainly to dominant A waves and reduced E waves. Conclusions. In patients on maintenance hemodialysis, the abnormal left ventricular inflow jet dynamics and early diastolic incoordinate long axis motion are unmasked by a preload reduction due to single hemodialysis in a different way from a transmitral Doppler flow pattern. [ABSTRACT FROM AUTHOR]

A kit using mouse monoclonal antibody against human alpha-fetoprotein (anti-AFP kit) has been developed. Cervical secretion (n = 34) and vaginal fluid (n = 15) was obtained from 30 pregnant volunteers. All 31 specimens obtained from women with intact membranes tested negative while all 18 specimens from women with premature rupture of membranes (PROM) tested positive. The newly developed kit allowed rapid and accurate diagnosis. We compared the kit results with those obtained by pH determination (nitrazine, bromthymol blue test) and measurement of AFP concentrations by enzyme-linked immunoassay (EIA). [ABSTRACT FROM AUTHOR]

A 5-year-old male with the Aarskog syndrome is described. He had abnormal facies, short stature, short fingers with interdigital webbing, a saddle type scrotum and mild mental retardation. In addition, he had isolated growth hormone deficiency as evidenced by the insulin, arginine, and propranolol-glucagon tests. An arginine test after short-term stimulation with estrogen further supported this diagnosis. His mother had minor abnormalities of the hands and feet, and slight mental retardation. [ABSTRACT FROM AUTHOR]

A 32-year-old man undergoing haemodialysis treatment for 10 years was referred to our hospital because of intractable heart failure with atrioventricular block. On the 5th hospital day he was found dead in bed. Autopsy revealed extensive metastatic calcification involving the myocardium and the cardiac conduction system, and a parathyroid adenoma with hyperplastic parathyroid glands. Retrospectively, first-degree heart block developed 14 months before death, and was subsequently associated with intraventricular conduction defect and atrioventricular block (Wenckebach type). Throughout the 3 years the patient received 1α-hydroxycholecalciferol (1α-OH-D3) and the calcium-phosphorus product (Ca×P) exceeded 70. 1α-OH-D3 should not be prescribed when patients develop an increase in Ca×P and exploration of the parathyroid glands should not be delayed if heart block presents in long-term haemodialyzed patients. [ABSTRACT FROM AUTHOR]

A patient with eight years' history of haemodialysis treatment developed gross haematuria. During evaluation severe abdominal pain with dyspnoea developed and he died suddenly. Autopsy revealed spindle cell type renal cell carcinoma (RCC) associated with acquired renal cystic disease and adenoma in the remaining kidney. Multiple embolization of RCC was considered to be linked to the cause of death. Although patients on long-term haemodialysis often have multiple renal cystic lesions, some of which are associated with tumour formation, RCC of this specific cell type in dialysed kidney has not been previously described. [ABSTRACT FROM AUTHOR]

Male rats received daily intraperitoneal injections of cadmium sulphate (2.0 mg/kg) for 3 (Cd-3 group), 6 (Cd-6 group) and 8 days (Cd-8 group). The blood samples were prepared for endothelin (ET)-1 assay, and the thoracic aorta was investigated by both electron microscopy and immunoelectron microscopy using anti ET-1 sera. The plasma ET-1 concentrations of both Cd-6 and Cd-8 groups increased significantly in a cumulative dose-dependent manner. The cadmium-treated rat aorta showed an increase in the number of Weibel-Palade (WP) bodies in endothelial cells, and degranulation and exocytosis of WP bodies occurred exclusively in the Cd-8 group. Immunoreaction for ET-1 was localized preferentially in WP bodies of both cadmium-treated and control groups, and in the rough endoplasmic reticulum of the cadmium-treated groups only. Reactivity was also found on the WP bodies undergoing exocytosis in the Cd-8 group. Cadmium intoxication induces an increase in number of ET-1-storing WP bodies in the rat aorta endothelium. The enhancement of extracellular release of their contents by exocytosis results in elevation of the plasma ET-1 concentration. [ABSTRACT FROM AUTHOR]

The case reported here is of a 61-year-old woman diagnosed with hepatopulmonary syndrome. She had had severe hypoxemia for 5 years. In room air, her arterial oxygen tension was low, and although we anticipated that treatment with oxygen would increase it, the treatment failed to do so. Pulmonary perfusion imaging with Tc-99m-labelled macroaggregated albumin showed an arterio-venous shunt in the lungs. Blood tests and liver scanning with Tc-99m-labelled galactosyl human serum albumin showed abnormalities of liver function, and per-rectal portal scintigraphy with Tc-99m pertechnetate showed severe portal hypertension. Inspection of a biopsy specimen taken under ultrasonographic guidance showed primary biliary cirrhosis of Scheuer stage I. The causes of hepatopulmonary syndrome are unknown, but seem to include a decrease in hepatic functional reserve, portal hypertension, or other factors. The development of hepatopulmonary syndrome due to portal hypertension in this patient is of interest. [ABSTRACT FROM AUTHOR]

Heated albumin microspheres with an average diameter of 45±8 μm and containing mitomycin C, released, in vitro, about 20% of this antibiotic over a 3-day period. VX-2 tumors were implanted into the hind leg of rabbits and the drug-containing microspheres were injected into the femoral artery of these animals. High levels of the drug were maintained for several hours in the tumor and growth of the tumor was inhibited considerably, compared to findings in control rabbits given the conventional mitomycin C. Half the number of the rabbits treated with our new method are alive with no evidence of tumor. [ABSTRACT FROM AUTHOR]

The genomic DNA and cDNA for a gene encoding a novel trehalose synthase (TSase) catalyzing trehalose synthesis from α- d-glucose 1-phosphate and d-glucose were cloned from a basidiomycete, Grifola frondosa. Nucleotide sequencing showed that the 732-amino-acid TSase-encoding region was separated by eight introns. Consistent with the novelty of TSase, there were no homologous proteins registered in the databases. Recombinant TSase with a histidine tag at the NH2-terminal end, produced in Escherichia coli, showed enzyme activity similar to that purified from the original G. frondosa strain. Incubation of α- d-glucose 1-phosphate and d-glucose in the presence of recombinant TSase generated trehalose, in agreement with the enzymatic property of TSase that the equilibrium lay far in the direction of trehalose synthesis. [ABSTRACT FROM AUTHOR]

The effects of Umklapp scattering on the zero-temperature conductance in one-dimensional quantum wires are reexamined by taking into account both the screening of external potential and the non-uniform chemical potential shift due to electron-electron interaction. It is shown that in the case away from half-filling the conductance is given by the universal value, 2 e 2/ h, even in the presence of Umklapp scattering, owing to these renormalization effects of external potential. The conclusion is in accordance with the recent claim obtained for the system with non-interacting leads being attached to a quantum wire. [ABSTRACT FROM AUTHOR]

A novel antitumor compound, N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea (HO-221) was evaluated for its antitumor activity in experimental tumor models. HO-221 preparation was given orally to tumor-bearing animals. The compound exhibited significant effects against various tumors such as P388 and L1210 leukemias; M5076 reticulum-cell sarcoma; colon 38 carcinoma; human xenografts MX-1, LX-1, GA-1, and Co-1; Lewis lung carcinoma; sarcoma 180; and Walker 256 carcinosarcoma and was especially effective against solid tumors. However, its effect on murine B16 melanoma was moderate. Intermittent administration of HO-221 produced better results. The effects of HO-221 on human tumor xenografts were compared with those of other antitumor agents. HO-221 showed activity against LX-1 lung and Co-1 gastrointestinal tumor and was also effective against advanced-stage L1210 leukemia and Lewis lung carcinoma. Furthermore, the effect of HO-221 on drug-resistant tumors was examined using murine leukemias L1210 and P388. It showed no cross-resistance with the known antitumor agents Adriamycin (ADM), daunomycin (DM), vincristine (VCR), mitomycin C (MMC), cisplatin (CDDP), 5-fluorouracil (5-FU), cytosine arabinoside (Ara-C), methotrexate (MTX), cyclophosphamide (CPA), or carboquone (CQ), and collateral sensitivity to HO-221 was found in MMC-, CDDP-, and CPA-resistant sublines. HO-221 exhibits significant reproducible, broad-spectrum antitumor activity against experimental tumors as well as human neoplasms. [ABSTRACT FROM AUTHOR]

In order to determine whether it is possible to reduce the toxicity of the nitrosoureas, including the delayed type of hematologic toxicity, without diminishing antitumor activity by administering the drug according to a new treatment schedule other than the single high-dose treatment schedule, we examined the antitumor activity against murine tumors and toxicities to host mice of a nitrosourea derivative, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1- nitrosourea hydrochloride (ACNU), which was administered according to two divided doses schedule. Experimental results indicated that the toxicity of ACNU with respect to lethality, as well as weight loss of host mice, was alleviated by administering ACNU (IV) at one-half of LD10 (20 mg/kg) on 2 successive days. However, no impairment of the antitumor activity of ACNU in various murine tumor systems was observed in comparison with that of ACNU administered according to the single high-dose schedule. The delayed type of hematologic toxicity (leukopenia) could not be alleviated by this treatment schedule. [ABSTRACT FROM AUTHOR]

To validate the usefulness of a human tumor-nude mice xenograft system as a potential model in the secondary screening of anticancer agents, the antitumor activity of 17 anticancer drugs has been studied in the treatment of a human breast cancer tumor (MX-1) transplanted to nude mice. For evaluation of the antitumor activity of the drugs we employed the LD10 predetermined in BDF1 mice as a standard therapeutic dose. Drugs were administered IV, IP, or PO, and antitumor activity was assessed by drug-induced growth inhibition measured by caliper. Among the 17 anticancer drugs, the most active compounds (maximum inhibition rate of tumor growth: greater than or equal to 90%) are mitomycin C, chromomycin A3, vincristine, vinblastine, vindesine, and hexamethylmelamine. Another group of compounds showed moderate activity (maximum inhibition rate of tumor growth: 89%-50%), these being adriamycin, daunomycin, mitoxantrone, bleomycin, 5-FU, 6-TG, and ftorafur. The remaining four drugs (peplomycin, cytosine arabinoside, 6-MP, and methotrexate) were inactive against the MX-1 tumor. These results suggested that in the nude mouse-human tumor xenograft system of the MX-1 tumor there was a good correlation between the antitumor activity of various anticancer drugs and their clinical efficacy; this system is therefore expected to be a useful model for the secondary screening system. [ABSTRACT FROM AUTHOR]

A new water-soluble nitrosourea derivative, 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077), was tested for antitumor activity against murine tumors and a human mammary carcinoma (MX-1) implanted in athymic mice, and the results were compared with those obtained with five other nitrosourea derivatives currently in clinical use: 1-(2-chloroethyl)-3-(methyl-alpha-D-glucopyranos-6-yl)-1-nitrosourea (MCNU), 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU), 3-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), chlorozotocin, and 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (Me-CCNU). [ABSTRACT FROM AUTHOR]

1,4-Dihydroxy-5,8-bis(((2-[(2-hydroxyethyl) amino] ethyl)amino))-9,10-anthracenedione dihydrochloride (mitoxantrone) was tested for antitumor activity against experimental tumors in mice and the results were compared with those of seven antitumor antibiotics: adriamycin (ADM), daunomycin (DM), aclarubicin, mitomycin C (MNC), bleomycin, neocarzinostatin, and chromomycin A3. The drugs were given IP or IV, in general on days 1, 5, and 9 following tumor inoculation. Mitoxantrone given IP at the optimal dose (1.6 mg/kg/day; as a free base) produced a statistically significant number of 60-day survivors (curative effect) in mice with IP implanted L1210 leukemia. The curative effect was not observed with any of the other antibiotics. In the case of IV implanted L1210 leukemia, there was an increase in lifespan (ILS) by more than 100% in the mice following IV treatment with mitoxantrone or DM. In IP implanted P388 leukemia, the curative effect was elicited by IP treatment with mitoxantrone or MMC. In IP implanted B16 melanoma, both the curative effect and a more than 100% ILS in mice that did die were produced by IP treatment with mitoxantrone or ADM. In SC implanted Lewis lung carcinoma, mitoxantrone and ADM administered IV also showed effective antitumor activities and produced a 60% and a 45% ILS, respectively. In conclusion, mitoxantrone and ADM had a wider spectrum of antitumor activity against mouse tumors, including two leukemias and two solid tumors, than did the other drugs; however, mitoxantrone elicited higher antitumor effects than ADM on mouse leukemias, especially on L1210 leukemias. Moreover, mitoxantrone possessed much higher therapeutic indices than ADM against IP implanted P388 (optimal dose/ILS40; greater than 128 versus 15.2) and L1210 (optimal dose/ILS25; 72.7 versus 4.8) leukemias. In addition, mitoxantrone showed moderate activity against DM-resistant L1210 leukemia. [ABSTRACT FROM AUTHOR]

Antibodies specific for the unique antigenic determinants of guinea pig fibrin (AGFA), which are distrinct from the antigenic determinants shared by both fibrinogen and fibrin, were isolated with appropriate immunosorbents from antisera produced in rabbits and goats by immunization with fibrin. The specificity of the purified goat AGFA was demonstrated by immunoelectrophoresis and by the double antibody precipitation method using I-labelled fibrinogen and antibodies to rabbit anti-goat IgG. The I-labelled AGFA were injected i.v. into inbred Sewall Wright strain 13 guinea pigs carrying the transplantable methylcholanthrene-induced sarcoma (MC-D) growing within a fibrin matrix, and were shown to be localized in the tumor tissue at a considerably higher concentration than in other organs. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate risk factors for the occurrence of fetal/neonatal passive immune thrombocytopenia (PIT) in pregnancy complicated with ITP. We studied 52 pregnancies with ITP and the 54 neonates retrospectively. Neonatal platelet counts were compared with maternal platelet counts, platelet-associated IgG (PAIgG) values and the presence of antiplatelet antibody in maternal circulation, history of previous PIT, maternal treatments for ITP, and other maternal/neonatal factors including gestational age and birth weight. Logistic regression analysis for multivariables was performed. PIT (platelet counts <100×103/μl) without neonatal mortality or any morbidity was observed in eight (15.4%) of 52 pregnancies. The presence of circulating antiplatelet antibodies in maternal blood, splenectomy prior to pregnancy, and a history of previous PIT were observed more frequently with statistical significance in women giving birth to neonates who developed PIT. By logistic regression analysis, splenectomy prior to pregnancy was found to be the single significant variable ( p=0.017, odds ratio 9.33) among the risk factors for PIT. Thus, splenectomy prior to pregnancy is related to increased risk for PIT in ITP-complicated pregnancy. [ABSTRACT FROM AUTHOR]

Thirty-nine pregnant women with idiopathic thrombocytopenic purpura (ITP) were studied in order to evaluate the influence of therapies for maternal ITP on fetal passive immune thrombocytopenia (PIT). Neonatal platelet counts were also compared with platelet counts, amount of PAIgG, and presence of circulating antiplatelet antibody in maternal blood. Eight of 41 neonates (19.5%) presented PIT without neonatal mortality. A higher incidence of PIT was observed in women with prior splenectomy than in women without splenectomy (66.7% vs 11.4%). Neither a therapeutic effect nor an increased risk of PIT was observed with steroids or gammaglobulin administration. No correlation was found between neonatal platelet counts and maternal platelet counts or maternal PAIgG, while positive cases for circulating antiplatelet antibody assay presented a higher incidence of PIT than negative cases. Additionally, a higher incidence of PIT was observed in women with a history of previous PIT than in women with a history of normal delivery. Prior splenectomy, presence of antiplatelet antibody in maternal blood, and a history of previous PIT seem to be risk factors for fetal PIT. [ABSTRACT FROM AUTHOR]

The surface array protein (SAP) of Campylobacter fetus strain TK is encoded by seven homologous sapA genes clustered on the chromosomal DNA. The spontaneously arising variant strain TK(SAP–) produces no SAP and carries an approximately 10-kb chromosomal deletion. To elucidate the mechanism underlying the loss of SAP synthesis, we analyzed the region containing the sapA homologues and the deletion. We constructed a physical map of the sapA cluster region by aligning the clones that contain sapA homologues. These analyses demonstrated that all sapA homologues were located within a limited region of about 50 kb of chromosomal DNA of strain TK. The TK(SAP–) deletion was located within this cluster and was 13.3 kb in size. The deletion occurred between two sapA homologues and resulted in the formation of a chimeric sapA homologue in the variant strain. Sequence analysis of the upstream regions and the conserved regions of all sapA homologues revealed a high degree of similarity. However, only one sapA homologue contained a putative promoter sequence. This promoter sequence was located in the deleted region. Thus, the deletion of the promoter appears to be responsible for the loss of SAP expression in TK(SAP–). [ABSTRACT FROM AUTHOR]

When PGH was administered intracerebroventricularly at doses of 5 and 15 nmoles in ethanol-anaesthetized rats, alcohol diuresis was inhibited and rectal temperature, blood pressure and heart rate were all significantly increased. [ABSTRACT FROM AUTHOR]

In vitro, taurine was shown to inhibit the decrease in the inotropic effect of ouabain at large doses in the normal and also low K medium in which this decrease in the inotropism of ouabain was facilitated. This inhibitory effect of taurine was, at least in part, due to the inhibition of the efflux of intracellular K in the isolated heart. [ABSTRACT FROM AUTHOR]

Under certain conditions, taurine (3.0 m M) potentiated cardiac contractile response to ouabain in the normal medium. The potentiation by taurine was also observed in the low K medium, in which the positive inotropic effect of ouabain increased. The potentiation as seen in both media was, at least in part, due to the increase by taurine of Ca content in the heart. Taurine in the heart was not directly related to this potentiation. [ABSTRACT FROM AUTHOR]

(1) The increased tissue catecholamine level of the thiamine deficient rat was shown in the atrium, the ventricle, the brain cortex and in the spleen but not in the brain stem and the adrenal gland. (2) The increased response to tyramine of the thiamine deficient heart is most probably due to the high catecholamine level caused by thiamine deficiency. (3) The increased catecholamine content in the thiamine deficient rat does not result from the increased pyruvic acid. [ABSTRACT FROM AUTHOR]

The eradication of invasive exotic species is desirable but often infeasible. Here, we show that male guppies are a potential biological agent for eradicating invasive mosquitofish through the mechanism of reproductive interference, which is defined as any sexual behavior erratically directed at a different species that damages female and/or male fitness. Together with decades of data on species distribution, our field surveys suggest that mosquitofish initially became established on Okinawa Island before being replaced by the more recently introduced guppies. More importantly, our laboratory experiments suggest that reproductive interference was one of the mechanisms underlying this species exclusion, and that in this case, the negative effects were asymmetric, i.e., they only impacted mosquitofish. Reproductive interference may offer a safer and more convenient method of biological control than the traditional sterile male release method because radiation is not necessary. [ABSTRACT FROM AUTHOR]

Two cases, one a 15-year-old girl and the other a 12-year-old girl, with goitrous hypothyroidism associated with elevated anti-DNA and antithyroid antibodies are reported. Abnormalities were noticed 1 year and 3 months and 5 years after the start of anticonvulsant therapy in case 1 and case 2, respectively. Alternation of drug (Valproate from ethosuximide) in case 1 resulted in disappearance of the goitre, and the thyroid function tests became normal. The titers of the antithyroglobulin and the antimicrosomal antibodies were reduced (below 1:100) from 1:400 and 1:1600, respectively. Discontinuance of anticonvulsant therapy and replacement therapy with desiccated thyroid in case 2 resulted in clinical improvement, reduction of antithyroglobulin antibody from 1:6400 to 1:400 and of antimicrosomal antibody from 1:409,600 to 1:25,600, and the thyroid function tests becoming normal. The present observations suggest that the anticonvulsants may induce or exacerbate autoimmune mechanisms in certain thyroid diseases. [ABSTRACT FROM AUTHOR]

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