Fatal fulminant hepatic failure associated with benzbromarone.
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Benzbromarone↗
Biomedical subjects
T Nakano
Publications and source records attributed to T Nakano.
Proliferation and cell death of embryonic primitive erythrocytes.
Erythropoietin (EPO) is the principal regulator for the production of adult-type definitive erythrocytes (EryD). EPO not only stimulates both the proliferation and differentiation of EryD progenitors, but also maintains the viability of EryD progenitors. Compared to the abundant knowledge about the function of EPO in EryD production, the roles of EPO in the production of embryonic-type primitive erythrocytes (EryP) are less clear. The effects of EPO on EryP proliferation and differentiation were investigated using EryP purified from developing mouse embryos and the cells obtained from mouse embryonic stem cells using an in vitro differentiation induction. Immature EryP of both in vivo and in vitro origin responded to EPO stimulation and underwent apoptosis with EPO deprivation. In contrast, there were no significant differences between the cultures with and without EPO, when fully mature EryP were examined, that is, EryP lost its dependency on EPO stimulation with maturation. These results show that EPO functions as a survival factor for immature embryonic EryP as well as immature EryD progenitors.
Animals↗
Sequential requirements for SCL/tal-1, GATA-2, macrophage colony-stimulating factor, and osteoclast differentiation factor/osteoprotegerin ligand in osteoclast development.
OBJECTIVE: Osteoclasts are of hematopoietic origin. The mechanism by which hematopoietic stem cells are specified to the osteoclast lineage is unclear. To understand the process of generation and differentiation of this lineage of cells, we performed in vitro studies on the differentiation of embryonic stem cells. MATERIALS AND METHODS: We examined the potential of mutant embryonic stem cell lines harboring targeted deletions of the GATA-1, FOG, SCL/tal-1, or GATA-2 genes to differentiate into osteoclasts and determined when these molecules function in osteoclast development. RESULTS: The lack of GATA-1 or FOG did not affect osteoclastogenesis. In contrast, SCL/tal-1-null embryonic stem cells generated no osteoclasts. In the case of the loss of GATA-2, a small number of osteoclasts were generated. GATA-2-null osteoclasts were morphologically normal and the terminal maturation was not disturbed, but a defect was observed in the generation of osteoclast progenitors. Experiments using specific inhibitors that block the signaling through macrophage colony-stimulating factor and osteoclast differentiation factor/osteoprotegerin ligand suggested that GATA-2 seems to act earlier in osteoclastogenesis than these cytokines. Interestingly, macrophage colony-forming units were not severely reduced by the loss of GATA-2 compared to osteoclast progenitors. CONCLUSION: These results indicate that osteocalsts need SCL/tal-1 at an early point in development, and that GATA-2 is required for generation of osteoclast progenitors but not for the later stages when macrophage colony-stimulating factor and osteoclast differentiation factor/ osteoprotegerin ligand are needed. We also demonstrated that osteoclast progenitors behave as a different population than macrophage colony-forming units.
Basic Helix-Loop-Helix Proteins↗
Modeling of signaling pathways for endocrine disruptors.
The so called endocrine disruptors have become an important working hypothesis for a wide range of toxicology researchers. This hypothesis has also attracted those who have worked on designer estrogens or selective estrogen receptor modulators. Already numbers of substances have been identified as such chemicals, but there remain a large number of chemicals waiting to be tested for their endocrine modulating capabilities. Because of the time and costs required for wet lab tests, it is unrealistic to apply these kinds of tests to all such suspicious or probable chemicals. Thus some theoretical methods must be developed for this purpose. However the conventional QSAR (quantitative structure activity relationships) approach is of limited relevance to this problem, because these methods do not take detailed mechanisms of molecular interactions in biological systems into account. Thus we have developed a database complex system that enables one to trace molecular interactions triggered by interaction of receptors with xenobiotic chemicals. The main components of this database complex are a potential endocrine disruptor database, a receptor database, a cell signaling networks database, a transcription factor database, and an affinity binding database based on modes of actions.
Database Management Systems↗
MR imaging of radiation osteitis in the sacroiliac joints.
The purpose of this study was to analyze magnetic resonance (MR) images of radiation osteitis of sacroiliac joints, retrospectively. Seven patients with radiation osteitis, which was diagnosed by pelvic plain radiographs and CT images, underwent MRI. T(1)-weighted spin echo images and T(2)-weighted fast spin echo images were obtained in all patients. Four patients were examined after gadolinium injection. Major signal changes of radiation osteitis were distributed on the iliac side. T(1)-weighted images showed diffuse low intensity both in sacral and iliac sides. T(2)-weighted images showed very low intensity adjacent to sacroiliac joints, but mixed intensity was illustrated apart from joints, and high intensity in the peripheral areas. Radiation osteitis showed slight to mild, but irregular enhancement in four patients after gadolinium administration. MRI can illustrate abnormal bone change distribution and is useful for diagnosing this entity by characteristic intensity patterns on T(1)-weighted images with and without gadolinium and T(2)-weighted image. However, the diagnosis of accompanied insufficiency fractures in the area of radiation osteitis is occasionally difficult with conventional MRI.
Aged↗
Morphological changes in mouse accessory sex glands following neonatal estrogen treatment.
A single injection of beta-estradiol 17-cypionate into the mice within 5 hr after birth induced inflammation in all prostate lobes and the seminal vesicles. Neutrophils emigrated into the lumen through the basal lamina and epithelium of the seminal vesicle and the anterior prostate. Local infiltration of lymphocytes was observed in the stroma and epithelium of ventral prostates. Lymphocytes penetrated through smooth muscle cells into epithelium. This could support the hypothesis that smooth muscle cells are the target of the estrogen action of prostates in estrogenized animals.
Animals↗
Identification of an antihypertensive peptide from peptic digest of wakame (Undaria pinnatifida).
A peptide fraction having activity against angiotensin I-converting enzyme (ACE) was separated from the peptic digest of protein prepared from wakame (Undaria pinnatifida) by ion-exchange chromatographies and gel-filtration. Fractions with high ACE inhibitory activity were combined and further chromatographed on a reverse-phase column to yield four tetrapeptides with ACE inhibitory properties. These tetrapeptides were identified by sequence analysis and fast atom bombardment mass spectrometry as Ala-Ile-Tyr-Lys (IC(50): 213 microM), Tyr-Lys-Tyr-Tyr (64.2 microM), Lys-Phe-Tyr-Gly (90.5 microM), and Tyr-Asn-Lys-Leu (21 microM). Each tetrapeptide was synthesized and its antihypertensive activity was determined after oral administration in spontaneously hypertensive rats. The blood pressure significantly decreased after tetrapeptide ingestion. The present study demonstrated that dietary wakame may have beneficial effects on hypertension.
Journal Article↗
Role of intracellular esterases in the production of esters by Acetobacter pasteurianus.
Esters are the major flavor compounds produced by Acetobacter sp. during vinegar production. The two genes encoding the esterases in the bacteria were disrupted, and the effects of the disruptions studied. When cultured in the presence of ethanol, the est1 gene-disrupted mutant (DE1K) did not produce any ethyl acetate or isoamyl acetate. However, the disruption of est2 did not affect the ester production. Ethyl acetate production by N-23 (pME122P) and DE1K (pME122P), which contain est1, was 1.7-fold higher than that by the wild type, N-23. On analyzing the relationship between ethyl acetate production and the extracellular ethanol and acetic acid concentrations, we found that the highest amount of ethyl acetate was produced when the molar ratio of ethanol and acetic acid was 1:1. These results indicate that the ester production by Acetobacter sp. is mostly catalyzed by the intracellular esterase, esterase-1, with ethanol and acetic acid used as the substrates.
Journal Article↗
Hepatocellular carcinoma associated with adult-type citrullinemia.
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Adult↗
Salt-induced exacerbation of morning surge in blood pressure in patients with essential hypertension.
The morning surge in blood pressure (BP) is related to the morning occurrence of lethal cardiovascular events. We tested the hypothesis that salt intake may be associated with the morning surge in BP in essential hypertension. Seventy-six patients were admitted and placed on a low salt diet (2 g/day) for 7 days followed by a high salt diet (20-23 g/day) for another 7 days. At the end of each salt diet, 24-h ambulatory BP and heart rate monitorings and head-up tilt (HUT) test were performed. Patients whose average mean BP (MBP) was increased by more than 10% by salt loading were assigned to the salt-sensitive (SS) group (n = 37); the remaining patients, whose MBP was increased by less than 10%, were assigned to the non-salt-sensitive (NSS) group (n = 39). The increase in ambulatory MBP during 6.30-8.00 am above the baseline (2.00-4.00 am) was significantly enhanced by salt loading in the NSS group (P < 0.05), but not in the SS group. The coefficient of variation of 24-h MBP and heart rate was increased by salt loading only in the NSS group. The significant elevation of plasma noradrenaline concentration after awakening, which was noted during the low salt diet period, was unchanged during the high salt diet period in the NSS group, but abolished in the SS group. Salt loading enhanced HUT-induced decrease in systolic BP without affecting the heart rate response only in the NSS group. We conclude that the morning surge in BP is enhanced by salt loading in the NSS type of essential hyper- tension, presumably by the excessive activation of the sympathetic nervous system. Journal of Human Hypertension (2000) 14, 57-64.
17-Hydroxycorticosteroids↗
Temporal order of sleepiness, performance and physiological indices during 19-h sleep deprivation.
Nineteen-hour variation of subjective sleepiness, performance and physiological indices were assessed during sleep deprivation. Longitudinal data of each index had its characteristic curve through which the values changed from day level to night level. A comparison of the time when each curve crossed its mid-range (50% value of its range) showed that those of subjective sleepiness and heart rate were significantly earlier than those of tracking error and coefficient of variation of R-R interval (CV(R-R)), P<0.01. That of rectal temperature was located at between 1:00 and 4:00 am. These temporal relationships were reproducible under two lighting conditions. These results will be useful in considering the occurrence of human errors by night-time workers in the early morning.
Adult↗
Effect of short duration morning bright light in elderly men: sleep structure.
Sleep structure was measured in five healthy elderly men in their homes. The subjects were exposed to bright light (6000 lx) for 30 min in the morning or instructed to sit in front of a desktop lighting device without light. Relative to the control conditions, bright light exposure significantly decreased time in bed and the number of awakenings. Rapid eye movement sleep was significantly fragmented by stage 1 sleep in the control condition compared with the bright light condition. These findings indicate that a short duration of morning bright light changes sleep structure and is effective in maintaining sleep.
Aged↗
Predicting the risk of pre-eclampsia and a small-for-gestational-age infant by quantitative assessment of the diastolic notch in uterine artery flow velocity waveforms in unselected women.
OBJECTIVES: To develop a new quantitative index, the notch depth index (NDI), to evaluate its association with the risk of pre-eclampsia and a small-for-gestational-age (SGA) infant and to compare its clinical usefulness with that of the uterine artery resistance index (RI) and the peak systolic to early diastolic velocity (A/C) ratio. METHODS: Uterine artery color Doppler ultrasound was performed in 288 consecutive healthy pregnant women at 20.2 +/- 2.0 (range 16.0-23.9) weeks of gestation. The NDI represents the depth of the early diastolic notch divided by the maximal diastolic velocity. RESULTS: Nine (3.1%) of the 288 women developed pre-eclampsia and 18 women (6.3%) delivered an SGA infant. The NDI was associated with subsequent onset of pre-eclampsia. The optimal cutoff value for the NDI in predicting pre-eclampsia was 0.14, giving a sensitivity, specificity and a positive predictive value (PPV) of 67, 92, and 22%, respectively. The PPV of the NDI was the largest of the three indices evaluated (12% for the RI and 16% for the A/C ratio). The relative risk for pre-eclampsia in women with values equal to or greater than the optimal cutoff values of the RI, A/C ratio and the NDI was 9.7 (95% confidence interval, 2.5-3.7), 19.2 (4.2-91), and 19.2 (5.1-71), respectively. The NDI of 0.14 improved the PPV of 18% determined by the presence of notches in bilateral uterine arteries. The optimal cutoff value of 0.14 for the NDI in predicting an SGA infant yielded a higher PPV (22%) than those for the RI (9%) and A/C ratio (12%). CONCLUSIONS: The NDI value in the second trimester is associated with the later onset of pre-eclampsia, and is clinically more useful in predicting pre-eclampsia than the two conventional indices.
Adult↗
Cell death induction by CTL: perforin/granzyme B system dominantly acts for cell death induction in human hepatocellular carcinoma cells.
Cell death induction by cytotoxic T lymphocytes (CTLs) is an important thesis for the understanding of tumor immunotherapy. In the current study we investigated the molecular machinery of CTL-induced cell death in human hepatocellular carcinoma cell lines (HCC lines). CTLs prepared from human peripheral blood induced cell death in all tested HCC lines. As the CTL-induced death system, the effectiveness of Fas ligand/Fas and/or Perforin/Granzyme B systems has been suggested, whereas cell death induction by CTLs was shown independently on Fas expression in the current study. Using various tetrapeptide inhibitors for caspase and its associated factor, we additionally demonstrated that inhibitors for caspase 3 (Ac-DEVD-CHO) and caspase 8/granzyme B (Ac-IETD-CHO) suppressed CTL-induced cell death, but an inhibitor for Fas-activated serine proteinase, which acts for the caspase 3 activator, did not, suggesting that CTL-induced cell death was initiated by the Perforin/Granzyme B system, rather than the Fas ligand/Fas system. On the basis of our current results, we report here that the Perforin/Granzyme B system acts dominantly for the cell death induction of HCC lines.
Animals↗
Survivin promotes cell proliferation in human hepatocellular carcinoma.
Survivin is a recently described inhibitor of apoptosis. Because suppression of apoptosis is important for carcinogenesis and tumor growth, we investigated the expression and function of survivin in human hepatocellular carcinomas (HCCs). We have shown that 4 HCC cell lines and 7 out of 8 human HCC tissues expressed survivin messenger RNA (mRNA), whereas expression of survivin mRNA was not detected in normal liver and nontumor areas of these tissues using the reverse transcription polymerase chain reaction. Survivin was detected primarily in the nucleus by immunofluorescence staining of HCC cells. In addition, 14 of 20 (70%) HCC tissues showed positive nuclear staining for survivin, whereas nontumor tissues showed little detectable staining by immunohistochemistry. Survivin expression strongly correlated with the proliferation index but not significantly with the apoptosis index in HCC tissues. Therefore, we performed cell cycle analysis after survivin transfection and showed that overexpression of survivin resulted in a decrease in the G(0)/G(1) phase and an increase in the S phase in all 4 HCC cell lines. Furthermore, we have found that survivin interacted with cyclin-dependent kinase 4 (Cdk4) and overexpression of survivin released p21(WAF1/Cip1) (p21) from Cdk4. From these results, we conclude that survivin promotes cell proliferation by interacting with Cdk4 and releasing p21 from Cdk4. This may play an important role in carcinogenesis and progression of human HCCs.
Apoptosis↗
Chemotherapeutic agents augment TRAIL-induced apoptosis in human hepatocellular carcinoma cell lines.
TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in various transformed cell lines but not in almost-normal tissues. It is regulated by 2 death receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2, and 2 decoy receptors, TRAIL-R3 and TRAIL-R4. We investigated the expression of TRAIL-R- and TRAIL-induced apoptosis in human hepatocellular carcinomas (HCCs). TRAIL-R1, -R2, and -R4 were expressed in 6 HCC cell lines examined, but TRAIL-R3 was expressed in only 2 of the 6 cell lines. In addition, immunohistochemical results revealed a high and prevalent expression of TRAIL-R1 and -R2 in human HCC tissues. Despite the expression of TRAIL-R1 and -R2, all 6 HCC cell lines showed resistance to TRAIL-induced apoptosis with no relation to nuclear factor kappa B (NF-kappaB) levels induced by TRAIL. TRAIL-induced death signal was inhibited with both decreased caspase-8 and caspase-3 activity. However, TRAIL induced significant apoptosis in the presence of a subtoxic level of actinomycin D, indicating that the TRAIL-induced apoptotic pathway is in place in these cell lines. In addition, we found that treatment with conventional chemotherapeutic agents, doxorubicin and camptothecin, dramatically augmented TRAIL-induced cytotoxicity in most of the HCC cell lines. Actinomycin D and camptothecin almost completely suppressed NF-kappaB induction by TRAIL, whereas doxorubicin had little effect. These results indicate that TRAIL, in combination with chemotherapeutic agents, may have therapeutic potential in the treatment of human HCC.
Antibiotics, Antineoplastic↗
Hepatocyte growth factor promotes cell survival from fas-mediated cell death in hepatocellular carcinoma cells via Akt activation and Fas-death-inducing signaling complex suppression.
The Akt/PI-3 kinase pathway is a system essential for cell survival. In the current study, we showed that hepatocyte growth factor (HGF) activates the Akt/PI-3 kinase pathway to suppress Fas-mediated cell death in human hepatocellular carcinoma (HCC; 3 lines; SK-Hep1, HLE, and Chang Liver cell lines), hepatoblastoma (1 line; HepG2), and embryonic hepatocyte (1 line; WRL). Five tested cell lines showed the resistance to Fas-mediated cell death by the pretreatment of HGF. This HGF-induced cell survival was suppressed by wortmannin (Akt/PI-3 kinase pathway inhibitor), suggesting an involvement of Akt. When cells were pretreated with HGF, Fas-mediated cell death was suppressed, followed by Akt phosphorylation at Ser473. Fas-death-inducing signaling complex (DISC) formation, especially FADD and caspase 8 interaction, was suppressed by HGF and the suppression of the Akt/PI-3 kinase pathway by transient expression of PTEN, resulting in acquisition of Fas-DISC formation and Fas-mediated cell death in HGF-treated cells. We suggest that HGF promotes cell survival in hepatocyte-derived cell lines (HCC, hepatoblastoma, and embryonic hepatocyte) from Fas-mediated cell death via Fas-DISC suppression as a result of Akt activation.
Carcinoma, Hepatocellular↗
Laparoscopic findings in an adult case of Alagille syndrome.
Laparoscopic findings in a 32-year-old woman presenting with Alagille syndrome are reported. The liver surface showed a segmental whitish discoloration on the surface of both lobes with a transverse sulcus which was not stained enough after an intravenous injection of indocyanine green (ICG). These findings suggested an acquired bile duct injury in addition to a congenital anomaly of the bile duct in this patient.
Adult↗