Deepwater formation in the North Pacific during the Last Glacial Termination.

Between approximately 17,500 and 15,000 years ago, the Atlantic meridional overturning circulation weakened substantially in response to meltwater discharges from disintegrating Northern Hemispheric glacial ice sheets. The global effects of this reorganization of poleward heat flow in the North Atlantic extended to Antarctica and the North Pacific. Here we present evidence from North Pacific paleo surface proxy data, a compilation of marine radiocarbon age ventilation records, and global climate model simulations to suggest that during the early stages of the Last Glacial Termination, deep water extending to a depth of approximately 2500 to 3000 meters was formed in the North Pacific. A switch of deepwater formation between the North Atlantic and the North Pacific played a key role in regulating poleward oceanic heat transport during the Last Glacial Termination.

[Effect of background factors concerning both elderly persons and their families with regard to the caregiver burnout in the home].

A cross sectional survey was performed to quantify factors that exhaust caregivers. We report that the degree of difficulty for caregivers correlated well with the burnout score (r = -0.517; p < 0.001), but the correlation between caregivers' burnout score and the level of their patient's basic ADL was lower (r = -0.317; p = 0.014). In this paper, we investigated other factors related to exhaustion. Caregivers' burnout score correlated with their age. The level of disease that caregivers complained increased burnout score. The need for nocturnal care and continuous observation, as well as rejection of aid burned out caregivers. Multiple regression analysis clarified that significant independent contributing factors for burnout score were help with toilet use, nocturnal aid and diseases suffered by caregivers.

Phase Ia study of a hypoxic cell sensitizer doranidazole (PR-350) in combination with conventional radiotherapy.

A phase Ia study of a 2-nitroimidazole nucleoside analog radiosensitizer doranidazole was conducted to evaluate its toxicity and pharmacokinetics in patients undergoing conventional external beam radiotherapy. Twenty-nine patients, aged 40-74 years, with a WHO performance status of 0-2 and with adequate organ functions, were entered in the study. Single administration of doranidazole was investigated first with 13 patients and then a course of five consecutive daily administrations was tested in 16 patients. Doranidazole was given i.v. 25 min before irradiation. Doranidazole doses of 400, 800, 1300 and 2000 mg/m2 were evaluated in the former study, and daily doses of 800, 1300 and 2000 mg/m2 were investigated in the latter study. All patients tolerated doranidazole administration. Although a transient decrease in the 24-h creatinine clearance rate was observed in five patients (one in the single administration study and four in the repeat administration study), this was not considered to be the dose-limiting toxicity. Other toxicities (hematological and gastrointestinal), which may not be related to doranidazole administration, were also mild and were not dose limiting. No neurotoxicity was observed. The average maximum concentration, area under the time-concentration curve and half-life of doranidazole in serum were 172-194 microg/ml, 502-582 microg x h/l and 4.2-4.6 h, respectively, at 2000 mg/m2. At the tested doses, administration of doranidazole was tolerable and achieved serum concentrations at which reasonable radiosensitization could be expected. A phase Ib/II study to evaluate the feasibility and efficacy of up to 30 repeat administrations seems to be warranted.

Prevalence of circulating antibodies to p10, a non-structural protein of the Borna disease virus in cats with ataxia.

Japanese domestic cats were surveyed for circulating antibodies to the plO and p24 proteins of the Borna disease virus (BDV) by Western blotting. Twenty-four of 52 cats (46.2%) with ataxia and other neurologic symptoms of unknown cause were positive for antibodies to BDV p10 and/or p24. In contrast, cats without neurological symptoms gave a significantly lower prevalence of anti-BDV antibodies to p10 and/or p24 (36 of 152 cats, 23.7%). Thirty specific pathogen-free (SPF) cats tested as controls were uniformly negative to BDV pl0 and p24 antigens. These results suggest that BDV may play a role in ataxia in cats. Additionally, our results suggest that it is necessary to use both p10 and p24 as antigens to detect circulating antibodies to BDV in cats.

Determination of the photochemical efficiency of o-quinodimethane ring closure in room-temperature solutions by using time-delayed, two-color photolysis technique

Photochemical efficiency of o-quinodimethane (3) ring closure at room temperature was determined by using a time-delayed, two-color photolysis technique. o-Quinodimethane (3) was generated by the photolysis of 1,2-bis[(phenylseleno)methyl]benzene (1) by a KrF (248 nm) laser pulse and thus-generated 3 was photolyzed by a subsequent XeCl (308 nm)/XeF (351 nm) laser pulse with varying delay time of 0 to 3 s. The time profile of 3 was monitored by the chemical analyses of benzocyclobutene (5) (a photochemical product of 3), which was formed by a one-photon process, and the spiro dimer of 3 (4) (a thermal product of 3) in the two-color photolysis experiments. The time profile of 3 followed a second-order decay kinetics. The photochemical efficiency was obtained by the analysis of the delay-time dependence of the product yields; those of the consumption of 3 and the conversion 3-->5 by a single pulse of the excimer laser were 81% and 5.7% for the XeCl laser, and 73% and 2.3% for the XeF laser. This difference was attributed to the different excited states involved in the photolysis. In contrast to the photolysis of 3 in argon or rigid organic matrixes, it was revealed that photochemical conversion 3-->5 was not the main path in the solutions, and intermolecular reactions predominated.

ArF and KrF laser-induced gas-phase photolysis of selenophene and tellurophene: extrusion of Te and Se and intramolecular 1,3-H shift competing with beta-C-C cleavage in C4H4 residue

ArF (193 nm) and KrF (248 nm) laser-induced photolysis of gaseous selenophene and tellurophene (C4H4M, M=Se and Te) has been examined. It is shown that, unlike thiophene and furan, selenophene and tellurophene cleave both M-C bonds and yield the elemental heteroatom (Se, Te), 1-buten-3-yne, and ethyne. The proposed mechanism involves an intermediate .HC=CH-CH=CH. diradical that decomposes via two competitive pathways, namely, 1,3-H shift to 1-buten-3-yne and beta-cleavage to two molecules of ethyne. It is shown that the relative importance of the channels depends both on the energy of the photon and on the heteroatom. Specifically, the 1,3-H shift/beta-cleavage ratios are 2.3 (193 nm, M=Se), 3.6 (248 nm, M=Se), 1.4 (193 nm, M=Te), and 10.5 (248 nm, M=Te). The inertness of the Te residuum and the high preference for the 1,3-H shift in KrF laser photolysis of tellurophene suggest that this photolysis can serve as a source of the C4H4 diradical for mechanistic studies.

[Effect of the level of basic activities of daily living on home caregiver burnout].

To relieve the stress of caregivers, it is critical to identify and classify the burden factors in the elderly patients. In order to determine the factors that exhaust caregivers, a cross sectional survey was done. The study employed a self-recording questionnaire form which included the Pines' burnout scale and the level of patient's basic activities of daily living (BADL). Seventy-three caregivers filled in the questionnaire. They reported the difficulty of care for an elderly patient in the home, and the degree of the difficulty correlated well with the burnout score (r = -0.517; p < 0.001). The caregivers' burnout score did not correlate so well with the level of their patient's BADL (r = -307; p = 0.014). Among the factors in BADL, aid for toilet use, feeding, sitting, and transferring raised the burnout scale. On the other hand, assistance for bathing and dressing did not correlate with the burnout score. On multiple regression analysis using the background factors for the burnout score as explanatory variables, aid for feeding and sitting were significant independent contributing factors. Since it became clear that the caregivers in the home were almost burnt out owing to the aid they need to give for the elderly person's BADL, attempts should be done to reduce their burden as soon as possible.

Primary hepatic carcinoid and neuroendocrine carcinoma: clinicopathological and immunohistochemical study of five cases.

Primary hepatic carcinoid and neuroendocrine carcinoma (NEC) are rare tumors. We experienced three carcinoids and two NEC originating in the liver during the past 25 years and attempted to elucidate the clinicopathological and immunohistochemical features of these tumors. The patients had no endocrine symptoms despite two of them having elevated plasma serotonin. Three of the five patients died of the tumor after operation with an average survival time of 20.6 months. All tumors were large (up to 26 cm in diameter), four of them solitary and one multinodular, and were not associated with liver cirrhosis. The carcinoid tumors showed insular, trabecular or glandular arrangement of argyrophilic cells, whereas in the NEC this histological pattern was distorted. Immunohistochemically the tumors showed expression of chromogranin A (all cases), chromogranin B (three cases), pancreastatin and chromostatin (four cases, respectively), prohormone convertase PC3 (three cases), carcinoembryonic antigen (CEA) and CA19-9 (two cases), cytokeratin 56 kDa (three cases), 160 kDa neurofilament (two cases) and neuron-specific enolase (two cases). Serotonin and glucagon were sporadically detected in two tumors. The most useful marker to confirm the diagnosis was chromogranin A, which was cleaved to pancreastatin and chromostatin in the tumor tissue, and was more reliable than other markers of neuroendocrine differentiation.

Large outbreak of swine influenza in southern Japan caused by reassortant (H1N2) influenza viruses: its epizootic background and characterization of the causative viruses.

In the winter of 1989 and the spring of 1990, there were large outbreaks of respiratory disease in two swine herds in Nagasaki Prefecture, southern Japan. Serological surveillance indicated that the majority of swine possessed antibodies to swine influenza virus H1 haemagglutinin and neuraminidase of early H3N2 influenza virus strains. Eight viruses were isolated from swine that showed typical clinical symptoms of influenza. The haemagglutinin and neuraminidase of these isolates were closely related to those of swine H1N1 and early human H3N2 viruses, respectively. At least two types of haemagglutinin antigens, distinguished by two monoclonal antibodies, were involved in the outbreaks. Evolutionary analyses indicated that the haemagglutinin gene of the H1N2 reassortants was closely related to those of a recent swine lineage (A/sw/HK/1/74 and A/sw/Ehime/1/80 viruses). However, the neuraminidase genes of the H1N2 reassortants were similar to those of swine N2 viruses which in turn are related to early human H3N2 viruses. A comparison of partial nucleotide sequences revealed that the six other genes of A/sw/Nagasaki/1/89 were derived from those of swine H1N1 virus.

Undifferentiated carcinoma of the duodenal ampulla.

This report demonstrates a case of undifferentiated carcinoma of the duodenal ampulla. A 74-year male experienced jaundice lasting for 3 weeks. An upper gastrointestinal series demonstrated a polypoid, ovoid filling defect in the second portion of the duodenum, and duodenoscopy disclosed a protruding mass involving the orifice of the papilla of Vater. Cholangiography demonstrated obstruction due to compression in the terminal common bile duct. Pylorus-preserving pancreatoduodenectomy was performed on the diagnosis of ampullary carcinoma. The gross specimen showed a polypoid mass, measuring 3.5 cm in diameter, in the ampulla, located mainly in the duodenal submucosal layer and invading the terminal common bile duct. Histologically, the tumor was small cell type, undifferentiated carcinoma, arising from the duodenal epithelium adjacent to the ampulla.

Comparison of false negative rates among breast cancer screening modalities with or without mammography: Miyagi trial.

False negative rates were compared in two screening modalities, physical examination with or without mammography, in an intervention study for women aged over 50 in Miyagi Prefecture. Thirty-five breast cancers were detected in 12,515 subjects who participated in the trial consisting of physical examination and mammography, whereas 44 breast cancers were detected in 50,105 subjects who received physical examination alone, so that the detection rates were 0.28% and 0.09%, respectively. Among 50,061 subjects who received physical examination alone, 8 women were diagnosed as having breast cancer within 12 months after the screening, while only one of 12,480 screenees receiving the combined modality was so diagnosed, implying false negative rates of 15.4% and 2.8%, respectively. When the screening sensitivity in the combined system was analyzed according to each single modality, the false negative rate provided by physical examination with mammography turned out to be 2.8%, significantly lower than that (33.3%) by the physical examination alone. Minimal breast cancers represented 25.7% of all screen-detected cancers in the combined modality, compared with 9.1% in the modality without mammography. The trial thus indicates that physical examination combined with mammography may be an appropriate modality for breast cancer screening in women aged over 50 on the basis of screening sensitivity.

Detection of the three common mutations of adeninephosphoribosyltransferase deficiency among Japanese.

We analyzed DNA from six Japanese patients with adenine phosphoribosyltransferase (APRT) deficiency who developed 2,8-dihydroxyadenine (DHA) urolithiasis. These six patients were selected for DNA analysis since they were expected to possess allele(s) with mutations other than two known abnormalities, i.e. a missense mutation at codon 136 (APRT*J allele) and a nonsense mutation at codon 98. In three of the six patients an insert of four bases CCGA was detected in exon 3 by sequencing clones obtained from the genomic DNA. In two of the three patients, both of the two alleles had this mutation (homozygotes) while the other patient had the APRT*J allele in addition to the allele with the 4-base insertion. To search for mutations other than the above three defined germline mutations, we amplified a genomic DNA segment including all the 5 exons of the APRT gene by PCR and cloned it into a plasmid. After selecting recombinant plasmids containing neither of the three defined mutations, we sequenced the entire APRT exons and introns. Abnormalities were found in neither the coding regions nor the exon-intron junctions. Disease-related mutations in these mutant alleles may exist in either 5' or 3' flanking sequences and remain to be elucidated.

[The efficacy of intra-arterial infusion chemotherapy in patients with non-resectable liver metastasis from colorectal cancer--a randomized study comparing FAM versus FEM].

The efficacy of FAM (5-FU, ADM, MMC) chemotherapy was compared with that of FEM (5-FU, EPIR, MMC) chemotherapy, in which the EPIR dose was about 1.3 times the ADM dose, by hepatic arterial infusion. Twenty-one patients with unresectable hepatic metastasis from colorectal cancer were the subjects of this multi-institutional randomized study. The response rate in evaluable 15 patients was 0% (0/6) in FAM group and 22% (2/9) in FEM group, with a 50% survival time of 15.3 months in FAM group and 15.1 months in FEM group. The major toxicities were gastrointestinal, together with hepatic dysfunction, both of which were not serious. Total incidence of > or = grade 2 toxicities was 50% (3/6) in FAM group and 80% (8/10) in FEM group. There was no statistical difference between the two groups in response rate, 50% survival time and toxicities. The clinical results of FAM and FEM were therefore considered equal, and an expected improvement in efficacy by increasing the EPIR dose was not confirmed. However, two patients in FEM group showed an objective response not observed in FAM group; one of them showed CR and survived about 3 years. These findings seem to suggest the efficacy of FEM hepatic arterial infusion chemotherapy for treatment of unresectable hepatic metastasis from colorectal cancer.

[A randomized trial of intrahepatic infusion chemotherapy for unresectable colorectal liver metastases. Sendai Study Group].

A prospective, controlled randomized trial of hepatic arterial infusion of 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin C (MMC) [FAM group] versus 5-FU, epirubicin (EPIR) and MMC [FEM group] in patients with unresectable liver metastasis from colorectal cancer is reported. No objective response was observed in FAM group (n = 6), while two objective responses, 1 complete and 1 partial (22.2%), were achieved in FEM group (n = 9). There was no significant difference in the 50% survival period between the two groups (468 days in FAM group (n = 8) versus 462 days in FEM group (n = 10). Long survival over 2 years was observed in FEM group, but not in FAM group. Toxicities were recorded in 50% (3/6) of FAM group, and 80% (8/10) of FEM group, but they were mild and well tolerated. In conclusion, although there was no significant difference in clinical effects between the two groups, the use of EPIR instead of ADR in combination with 5-FU and MMC might be favorable for intrahepatic infusion chemotherapy because responders and long-term survival were exclusively observed in FEM group.

[Functional and phenotypic analysis of tumor infiltrating lymphocytes derived from solid tumors and effusion associated lymphocytes in malignant ascites cultured in recombinant interleukin 2].

Tumor infiltrating lymphocytes (TIL) and effusion associated lymphocytes (EAL) were isolated from 7 human solid tumors and 6 malignant ascitic fluids respectively, and cultured in rIL2 (700JRU/ml)-containing medium. Long-term culture (> 14 days) of separated lymphocytes with exponential increase in cell number was achieved in 5 EAL-cultures, whereas in only 2 TIL-cultures. rIL2-expanded TIL and EAL manifested significant cytotoxicity in a 4-hrs chromium release assay. The maximum NK and LAK activity were reached 21 days and 14 days after starting incubation with rIL2 respectively, followed by a rapid decrease in cytolytic potential without declining growth rate of the cells. Phenotypic analysis showed the majority of the freshly isolated TIL and EAL were CD3+ T cells, and CD16+ NK cells were rarely identified in TIL. With induction of LAK cell activity, CD8+ T cells predominantly increased in TIL-cultures, while both CD4+ and CD8+ T cells and CD16+ NK cells were increased in EAL cultures. In activated TIL most cytolytic activity was found in CD8+ T cells, in contrast CD16+ NK cells were responsible for it in activated EAL. These results indicated that EAL and TIL have similar properties in which they coexist with cancer cells at tissue level and were capable of expanding and acquiring LAK cell activity in the presence of rIL2, but apparently differ in their mechanism of rIL2-mediated activation.

Improved detection rate of early breast cancer in mass screening combined with mammography.

A cohort study to compare mass screening with and without mammography was conducted in Miyagi Prefecture, Japan in order to establish whether the effectiveness of breast cancer screening would be improved when mammography was combined with physical examination. A trial of mass screening combined with mammography was carried out in 9634 women aged over 50. Lateral imaging of the breast using single-view film mammography was performed at the first stage of mass screening in addition to physical examination of the breast. Results in the trial were compared with those obtained in 35511 age-matched subjects without mammography. Thirty breast cancers were found in the trial with a detection rate of 0.31%, which was much higher than that (0.08%) obtained by physical examination without mammography. In 15 of the 30 patients the breast tumor was not palpated at the first screening, but abnormal findings were detected in the mammography. A higher rate (73%) of early breast cancer was obtained in the screening trial with mammography than that (39%) obtained in the screening with physical examination alone. Mass screening combined with mammography is superior to that without mammography for breast cancer screening, especially for the detection of non-palpable, early breast cancer.