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21.
Eiji Takeuchi Yuji Nimura Shin-ichi Mizuno Hideaki Suzuki Shinsuke Iyomasa Masaki Terasaki Hiroshi Kuriki Keiko Tamiya-Koizumi Shonen Yoshida 《Journal of Hepato-Biliary-Pancreatic Surgery》1997,4(3):254-262
Hepatocyte regeneration has been widely investigated, with the mitotic index and the incorporation of [3H]thymidine being used as regeneration markers. We focused on the induction of DNA replication enzymes, particularly DNA polymerases
(pol) α, δ, and ε. Using rat models, we have shown that the activity of pol α in crude liver extract well represents the regenerating
capacity of hepatocytes. Using pol α as an indicator, we analyzed liver regeneration in rat models under various conditions:
obstructive jaundice, external or internal biliary drainage, and the obstruction of portal vein branches. It has been revealed
that the ligation of the common bile duct alone induces a certain amount of hepatocyte proliferation. It was striking that
external biliary drainage suppressed regeneration capacity in cholestatic rat liver after partial hepatectomy. The strong
regeneration in nonligated lobes induced by portal branch ligation was similar to the liver regeneration seen after partial
hepatectomy with respect to the induction of DNA polymerases. Taken together, the aspects of DNA replication, particularly
the induction of DNA polymerases, may contribute to shedding new light on the regeneration of human liver.
This work was supported in part by a Grant-in-Aid for General Scientific Research and for Cancer Research from the Ministry
of Education, Science and Culture, Japan, and by grants from the Uehara Memorial Foundation 相似文献
22.
Rolf W. Hartmann Martin Frotscher Dorothea Ledergerber Gerald A. Wchter Gertrud L. Grün Tom F. Sergejew 《Archiv der Pharmazie》1996,329(5):251-261
In search of potential drugs for the treatment of estrogen- and androgen-dependent cancer as well as the prophylaxis of metastases, tetralones, tetralins, and dihydronaphthalenes bearing a OCH3 substituent at the benzene nucleus and an imidazol-4-yl, imidazol-1-yl, or 1,2,4-triazol-1-yl substituent in 2-position were synthesized with and without C1-spacer between the rings (compounds 2 – 26 ). The compounds were tested in vitro for inhibition of the three target enzymes P450 arom (human placental microsomes), P450 17 (rat testicular microsomes), and P450 TxA2 (citrated human whole blood). To examine selectivity, some compounds were further tested in vitro for inhibition of P450 18 (bovine adrenal mitochondria), P450 see (bovine adrenal mitochondria) and corticoid formation (aldosterone, corticosterone; ACTH stimulated rat adrenal tissue). In vivo, selected compounds were examined in Sprague Dawley rats regarding P450 TxA2 inhibition, reduction of plasma testosterone concentration, antiuterotrophic activity (inhibition of the uterotrophic activity of androstenedione), reduction of plasma estradiol concentration (pregnant mares' serum gonadotropin-primed rats), and mammary tumor inhibiting activity (dimethylbenzanthracene-induced tumor; pre- and postmenopausal model). In the series of imidazol-4-yl compounds, which represent a novelty in the field of azole inhibitors of steroidogenic P450 enzymes, strong inhibitors of P450 arom and/or P450 17 were found: 7-OCH3-2-(imidazol-4-ylmethylene)-1-tetralone ( 4 ) and 7-OCH3-2-(imidazol-4-ylmethyl)-tetralin ( 12 ) are among the most potent inhibitors of P450 arom in vitro known so far. Compound 4 is a selective inhibitor, whereas 12 shows in addition strong inhibition of P450 17. In contrast to 12 , the 6-OCH3 derivative (compound 11 ) is a selective inhibitor of P450 17, being 50 times more potent than ketoconazole. Some imidazol-1-yl compounds show a marked inhibition of P450 TxA2: 2-(imidazol-1-ylmethyl)-1-tetralone ( 13 ) is a selective inhibitor of P450 TxA2, whereas 7-OCH3-2-(imidazol-1-ylmethyl)-tetralin ( 17 ) as well as 2-(imidazol-1-ylmethyl)-tetralin ( 16 ) and 7-OCH3-2-imidazol-1-yl-3,4-dihydronaphthalene ( 25 ) additionally show strong inhibition of P450 arom and P450 17. Regarding the other steroidogenic P450 enzymes as well as corticosterone formation, the compounds show only little inhibitory activity. Aldosterone formation, however, is inhibited at low concentrations. Nevertheless, 4 and 12 are more selective, i.e. inhibit aldosterone synthesis less than the well known inhibitor of P450 arom fadrozole. The compounds show activity in the aforementioned in vivo tests. 相似文献
23.
K Kondoh S Sasaki T Oku S Minohara S Hasegawa Y Sawada M Morita A Takeuchi 《Kyobu geka. The Japanese journal of thoracic surgery》1992,45(7):565-9; discussion 569-72
In six hundred and six consecutive patients undergoing coronary artery bypass grafting (CABG) within the past 17 years (May 1974 to March 1991), repeated CABG were performed on 10 patients (1.65%). The main reasons for repeated CABG were graft failure (GF) in 8, progression of native disease (NP) in 5 and incomplete revascularization (IR) in 3 patients. The incidence of GF was high either within a half year or around 5 years after CABG. Although all patients survived from reoperation, four patients continued to have mild angina pectoris. When the recurrence of angina is noted after CABG, coronary arteriography and if necessary PTCA should be done as soon as possible. If a second surgery is inevitable, maximum utilization of arterial graft and accomplishment of complete revascularization are emphasized. 相似文献
24.
Gary Coleman Tom A. Gardiner Ariel Boutaud Alan W. Stitt 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2007,245(4):581-587
Background A recombinant form of the α2(IV)NC1 domain of type IV collagen has been shown to have potent anti-angiogenic activity although
this peptide has not been studied in the context of proliferative retinopathies. In the current investigation we examined
the potential for α2(IV)NC1 to regulate retinal microvascular endothelial cell function using a range of in vitro and in vivo
assay systems.
Materials and methods α2(IV)NC1 at concentrations between 0.1 and 1 μg/ml was added to retinal microvascular endothelial cells (RMECs) followed
by assessment of cell attachment, proliferation and survival. This agent was also tested within a novel in vitro three-dimensional
retinal angiogenesis assay and the number of angiogenic sprouts quantified. α2(IV)NC1 was also delivered intra-vitreally to
mice with oxygen-induced proliferative retinopathy (OIR) and neovascularisation evaluated in comparison with vehicle-treated
controls.
Results RMECs treated with α2(IV)NC1 (0.1, 0.5 and 1 μg/ml) showed delayed attachment at 3 h post-seeding, although this deficit had
been restored at the 6-h time point. BrdU assay of DNA replication revealed that confluent RMECs treated with α2(IV)NC1 showed
no measurable response in comparison with vehicle-treated controls. By contrast, proliferation of sub-confluent RMECs was
significantly reduced by α2(IV)NC1 at 0.5 μg/ml (P<0.01). α2(IV)NC1 also induced apoptosis in RMECs and inhibited angiogenesis of pre-existing retinal vascular networks in
vitro (P<0.001). Intra-vitreal injection of α2(IV)NC1 in the OIR model significantly inhibited pre-retinal neovascularisation compared
with vehicle-treated controls (P<0.001).
Conclusion α2(IV)NC1 inhibits angiogenesis in the retinal microvasculature. This recombinant protein has potential for the treatment
of neovascularisation in proliferative retinopathies.
BioStratum Inc. did not sponsor this research in any way. None of the authors are paid consultants with this company. 相似文献
25.
T Okamura T Takeuchi O Nishii T Yaginuma T Kawana 《Nippon Sanka Fujinka Gakkai zasshi》1987,39(11):2059-2065
Ten puerperal women were put on a 1,200 kcal diet per day for 3 days followed by an ordinary 1,800 kcal diet per day for 3 days [Low-Caloric (LC) group]. Fifteen puerperal women were put on an ordinary 1,800 kcal diet per day for 6 days[Ordinary-Caloric (OC) group]. All of the women took breakfast at 7:30 am, blood was drawn at 9:30 am and then the breasts were milked for 2 minutes with an electric breast pump starting on the day of delivery (Day 0) and continuing to Day 5. Four women in the LC and OC groups underwent a thyrotropin-releasing hormone (TRH) stimulation test on Days 1 and 3. Serum prolactin (PRL) and TSH levels in the LC group tended to be much lower than those of the OC group during the test period. Serum PRL and TSH release response to TRH in the OC group were much higher than in the LC group on Days 1 and 3. No significant difference was noted between the OC and LC groups in serum estradiol (E2) and cortisol levels from Day 0 to Day 5. The milk volume in the LC group was significantly less than in the OC group on Day 1. Analysis of milk specimen components revealed little difference between the OC and LC groups. These results suggested that a low-caloric diet may suppress PRL, TSH and milk secretion and may not be useful for breast-feeding. 相似文献
26.
Margaret Hogg Maxine Braithwaite Michael Bailey Tom Kotsimbos John W Wilson 《Journal of cystic fibrosis》2007,6(3):223-227
With increasing numbers of cystic fibrosis (CF) patients surviving to adulthood, issues related to vocation inevitably arise and warrant specific attention. We examined the percentage of participants with CF currently working and explored risk factors for work disability among adults with CF. METHOD: We recruited 50 consecutive patients from an adult cystic fibrosis service. Demographic, employment history, illness severity indicators and CF-attributed work disability factors were evaluated. Demographic risk factors for work disability using the illness severity measures of FEV(1), S-K score, CRDQ, and recent hospitalisation as independent variables were determined. RESULTS: Factorial analysis of a disability index (DI) indicated no dependency on FEV(1) or S-K score, but dependency on quality of life indices (p<0.05), age (p<0.05) and hospital admission rate (p<0.05). Hours worked per week were dependent on quality of life (p<0.01) (mastery of disease domain), fewer hospital admissions (p<0.01) and age (p<0.05). Sixty-eight percent of the sample reported that CF resulted in significant impediments to employment. However, few had sought vocational guidance (6%). CONCLUSION: Determinants of workforce participation shows that hours worked and perceived disability are more dependent on mastery of disease, age, and time in hospital, than on clinical severity scores. Health professionals may assist productivity through career counselling or tailored programs. 相似文献
27.
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29.
Emma L Wignall Jon M Dickson Paul Vaughan Tom F D Farrow Iain D Wilkinson Michael D Hunter Peter W R Woodruff 《Neuropsychopharmacology》2004,56(11):832-836
BACKGROUND: Previous structural magnetic resonance (MR) research in patients with posttraumatic stress disorder (PTSD) has found smaller hippocampal volumes in patients compared with control subjects. These studies have mostly involved subjects who have had PTSD for a number of years, such as war veterans or adult survivors of childhood abuse. Patients with recent-onset PTSD have rarely been investigated. To our knowledge only one other study has investigated such a group. The aim of this study was to compare hippocampal volumes of patients with recent onset PTSD and nontrauma-exposed control subjects. METHODS: Fifteen patients with PTSD, recruited from an accident and emergency department, were compared with 11, non-trauma-exposed, healthy control subjects. Patients underwent a structural MR scan soon after trauma (mean time = 158 +/- 41 days). Entire brain volumes, voxel size 1 x 1 x 1 mm, were acquired for each subject. Point counting and stereology were used to measure the hippocampal and amygdala volume of each subject. RESULTS: Right-sided hippocampal volume was significantly smaller in PTSD patients than control subjects after controlling for effects of whole brain volume and age. Neither left nor total hippocampal volume were significantly smaller in the PTSD group after correction. Whole brain volume was also found to be significantly smaller in patients. There were no differences in amygdala or white matter volumes between patients and control subjects. CONCLUSIONS: This result replicates previous findings of smaller hippocampal volumes in PTSD patients, but in an underinvestigated population, suggesting that either smaller hippocampal volume is a predisposing factor in the development of PTSD or that damage occurs within months of trauma, rather than a number of years. Either of these two hypotheses have significant implications for the treatment of PTSD. For instance, if it could be shown that screening for hippocampal volume may, in some cases, predict those likely to develop clinical PTSD. 相似文献
30.