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Biomedical subjects

H Niwa

Publications and source records attributed to H Niwa.

At least 55 records · Page 3Linked to original sources
PubMed2000

Cardiovascular responses to epinephrine-containing local anesthetics for dental use: a comparison of hemodynamic responses to infiltration anesthesia and ergometer-stress testing.

OBJECTIVE: Cardiovascular effects of infiltration anesthesia have been documented in numerous studies. However, few studies have been carried out to compare the effects of infiltration anesthesia with the effects of exercise-stress testing. The purpose of this study was to examine this issue. STUDY DESIGN: Eight young and 13 older subjects were given infusions of epinephrine to produce cardiovascular responses comparable with those found in subjects undergoing infiltration anesthesia with 3.6 mL of lidocaine with 1:80,000 epinephrine (L-E). Cardiovascular responses to this drug treatment were evaluated with echocardiography and compared with those produced by ergometer exercise. RESULTS: The hemodynamic effects of L-E infiltration anesthesia were less than those produced by ergometer-stress testing at 25 watts (W) in young subjects and at 15 W in the older subjects. The workload of this ergometer-stress testing was about 4 metabolic equivalents (METS), which is approximately equivalent to the workload of walking 4.8 km/hr, doing light yard work (ie, raking leaves, weeding, or pushing a power mower), painting, or doing light carpentry. CONCLUSION: With the exception of some specific pathologic conditions, such as serious arrhythmia, infiltration anesthesia with 3.6 mL of L-E can be carried out safely on the patients who have exercise capacity of more than 4 METS.

Adult↗
PubMed1999

Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice.

Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) receptor gene (GIPR) were generated to determine the role of GIP as a mediator of signals from the gut to pancreatic beta cells. GIPR-/- mice have higher blood glucose levels with impaired initial insulin response after oral glucose load. Although blood glucose levels after meal ingestion are not increased by high-fat diet in GIPR+/+ mice because of compensatory higher insulin secretion, they are significantly increased in GIPR-/- mice because of the lack of such enhancement. Accordingly, early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes.

Administration, Oral↗
PubMed1999

Nerve growth factor prevention of aged-rat sympathetic neuron injury by cisplatin, vincristine and taxol--in vitro explant study.

We examined the preventive effects of nerve growth factor (NGF) against neurotoxicity induced in aged rats by anticancer drugs such as cisplatin, vincristine and taxol using a superior cervical ganglion explant culture system. The inhibition of neurite outgrowth by cisplatin, vincristine and taxol was markedly prevented by co-treatment with NGF. The neurite and nerve cell populations were well preserved in vincristine and taxol, whereas cisplatin reduced these populations as compared with control even when treated with NGF. These results indicate that, just as in young adult rats, NGF prevents toxic sympathetic nerve injury induced by vincristine and taxol even in aged rats, but does not protect against cisplatin-induced nerve cell injury.

Aging↗
PubMed1999

Differential regulation of mammalian period genes and circadian rhythmicity by cryptochromes 1 and 2.

Cryptochromes regulate the circadian clock in animals and plants. Humans and mice have two cryptochrome (Cry) genes. A previous study showed that mice lacking the Cry2 gene had reduced sensitivity to acute light induction of the circadian gene mPer1 in the suprachiasmatic nucleus (SCN) and had an intrinsic period 1 hr longer than normal. In this study, Cry1(-/-) and Cry1(-/-)Cry2(-/-) mice were generated and their circadian clocks were analyzed at behavioral and molecular levels. Behaviorally, the Cry1(-/-) mice had a circadian period 1 hr shorter than wild type and the Cry1(-/-)Cry2(-/-) mice were arrhythmic in constant darkness (DD). Biochemically, acute light induction of mPer1 mRNA in the SCN was blunted in Cry1(-/-) and abolished in Cry1(-/-)Cry2(-/-) mice. In contrast, the acute light induction of mPer2 in the SCN was intact in Cry1(-/-) and Cry1(-/-)Cry2(-/-) animals. Importantly, in double mutants, mPer1 expression was constitutively elevated and no rhythmicity was detected in either 12-hr light/12-hr dark or DD, whereas mPer2 expression appeared rhythmic in 12-hr light/12-hr dark, but nonrhythmic in DD with intermediate levels. These results demonstrate that Cry1 and Cry2 are required for the normal expression of circadian behavioral rhythms, as well as circadian rhythms of mPer1 and mPer2 in the SCN. The differential regulation of mPer1 and mPer2 by light in Cry double mutants reveals a surprising complexity in the role of cryptochromes in mammals.

Animals↗
PubMed1999

Constructing adenoviral vectors by using the circular form of the adenoviral genome cloned in a cosmid and the Cre-loxP recombination system.

Recombinant adenoviral vectors have been generated either by the in vivo homologous recombination method or by the in vitro direct ligation method. However, the efficiency of adenoviral vector construction by these methods is low, because of the large size of the recombinant vectors. To improve the ease of constructing adenoviral vectors, we used the circular form of adenoviral DNA, which can generate infectious viruses with an efficiency comparable to that of virion DNA, after transfection into 293 cells constitutively producing adenovirus E1 protein. We replaced the E1 region of the circular form of adenoviral DNA with a cosmid vector flanked by loxP sites, resulting in a 41-kb cosmid, designated pALC. An expression cassette that bicistronically expresses IL-5 and green fluorescent protein (GFP) was readily inserted between the loxP-flanked cosmid backbone and the adenoviral genome of pALC, using the cosmid vector cloning system. Transfection of the resulting cosmid into 293 cells did not produce any infectious adenoviruses because its size (46 kb) was larger than the packing capacity of the adenoviral particles. However, cotransfection of a Cre-expression plasmid with this cosmid into 293 cells efficiently excised the loxP-flanked cosmid vector backbone, and produced the adenoviral vector expressing IL-5 and GFP. To simplify our method further, we have produced a 293 cell line constitutively expressing Cre recombinase. Transfection of pALC cosmid alone into this cell line efficiently generated adenoviral vector. The adenoviral vector construction method presented here is simple and efficient and should further facilitate the application of recombinant adenoviral vectors for in vivo and in vitro gene transfer.

Adenoviridae↗
PubMed1999

Assessment of extensive surgery for locally advanced lung cancer. Safety and efficacy of induction therapy.

OBJECTIVE: Locally advanced lung cancer has a poor prognosis, despite extensive surgery conducted in an effort to improve survival. We evaluated the safety and efficacy of induction therapy prior to extensive surgery for locally advanced lung cancer. METHODS: Primary resection for lung cancer was done in 549 consecutive patients divided into three groups; 446 undergoing standard pulmonary resection (no extensive surgery), 87 undergoing extensive surgery without induction therapy, and 16 undergoing surgery after induction therapy. RESULTS: Morbidity was 23.5%, 28.6%, and 43.8%, respectively. The rate was significantly higher in the induction group compared with the no extensive surgery group (P < 0.05). Surgical mortality was 0.67%, 3.4%, and 6.3%, respectively. The difference was statistically significant between the no extensive surgery and extensive surgery groups (P < 0.02), and between the no extensive surgery and induction groups (P < 0.02). Hospital mortality was 2.2%, 9.2%, and 6.3%, respectively. The rates were significantly higher in the extensive surgery (P < 0.01) and induction (P < 0.05) groups compared to the no extensive surgery group. Five-year survival was 50.3% for the patients who received induction therapy, and 14.7% for the patients who did not receive induction therapy. CONCLUSIONS: Survival differences between the induction and non induction groups were not significant, but some patients with T3 or T4 disease may benefit from induction therapy. The high morbidity of induction treatment should be recognized, and strict candidate selection and careful postoperative care used to help prevent increased mortality.

Adenocarcinoma↗
PubMed1999

Experimental determination of the safe minimum perfusion flow rate for low-flow hypothermic cardiopulmonary bypass.

This study investigated the safe minimum perfusion flow rate for low-flow hypothermic cardiopulmonary bypass in a canine model. The adequacy of cerebral oxygenation was determined from the adenosine concentration, the oxygen saturation of cerebral venous blood and brain oxyhemoglobin level. In experiment 1, nine beagles were cooled on bypass to a nasopharyngeal temperature of 18 degrees C and the perfusion flow rate was reduced in a stepwise fashion every 30 min from 100 to 50, 30, 20 and 10 ml/kg per min. In experiment 2, six beagles were cooled on bypass as in experiment 1, and flow was maintained at 30 ml/kg per min for 120 min. At a perfusion flow rate of 30 ml/kg per min, adequate cerebral oxygenation was maintained for 120 min. In contrast, perfusion flow rates of 20 and 10 ml/kg per min were associated with cerebral ischemia.

Adenosine Triphosphate↗
PubMed1999

Low-potassium University of Wisconsin solution for cardioplegia: improved protection of the isolated ischemic neonatal rabbit heart.

Recovery of cardiac function and high-energy phosphates following ischemia and reperfusion were determined for hearts perfused with low potassium University of Wisconsin solution, high potassium University of Wisconsin solution, St Thomas' solution, or subjected to hypothermia alone. Isolated hearts were arrested for either 3 h at 15 degrees C or 6 h at 20 degrees C (n = 7 for each group) with one of the four solutions and then reperfused. Aortic flow after ischemic arrest at 20 degrees C was 40.3 +/- 13.3%, 79.3 +/- 10.0%, 64.3 +/- 11.9% and 43.9 +/- 15.9% of control values for high potassium University of Wisconsin solution, low potassium University of Wisconsin solution, St Thomas' solution and hypothermia alone, respectively. Similar results were observed in hearts subjected to ischemic arrest at 15 degrees C. Myocardial adenosine triphosphate and creatine phosphate after reperfusion tended to be higher in the low potassium University of Wisconsin solution group. It is concluded that low potassium University of Wisconsin solution may provide reliable cardioplegia during surgery that requires prolonged cardiac arrest in neonates and infants.

Adenosine↗
PubMed1999

Signaling mechanisms regulating self-renewal and differentiation of pluripotent embryonic stem cells.

An ability to propagate pluripotent embryonic cells in culture is the foundation both for defined germline modification in experimental rodents and for future possibilities for broad-based cellular transplantation therapies in humans. Yet, the molecular basis of the self-renewing pluripotent phenotype remains ill-defined. The relationship between factors that influence embryonic stem cell propagation in vitro and mechanisms of stem cell regulation operative in the embryo is also uncertain. In this article we discuss the role of intracellular signalling pathways in the maintenance of pluripotency and induction of differentiation in embryonic stem cell cultures and the mammalian embryo.

Animals↗
PubMed1998

Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4.

Oct4 is a mammalian POU transcription factor expressed by early embryo cells and germ cells. We report that the activity of Oct4 is essential for the identity of the pluripotential founder cell population in the mammalian embryo. Oct4-deficient embryos develop to the blastocyst stage, but the inner cell mass cells are not pluripotent. Instead, they are restricted to differentiation along the extraembryonic trophoblast lineage. Furthermore, in the absence of a true inner cell mass, trophoblast proliferation is not maintained in Oct4-/- embryos. Expansion of trophoblast precursors is restored, however, by an Oct4 target gene product, fibroblast growth factor-4. Therefore, Oct4 also determines paracrine growth factor signaling from stem cells to the trophectoderm.

Animals↗
PubMed1998

Pancreatic beta cell-specific expression of thioredoxin, an antioxidative and antiapoptotic protein, prevents autoimmune and streptozotocin-induced diabetes.

The cytotoxicity of reactive oxygen intermediates (ROIs) has been implicated in the destruction of pancreatic beta cells in insulin-dependent diabetes mellitus (IDDM). Thioredoxin (TRX), a redox (reduction/oxidation)-active protein, has recently been shown to protect cells from oxidative stress and apoptosis. To elucidate the roles of oxidative stress in the development of autoimmune diabetes in vivo, we produced nonobese diabetic transgenic mice that overexpress TRX in their pancreatic beta cells. In these transgenic mice, the incidence of diabetes was markedly reduced, whereas the development of insulitis was not prevented. Moreover, induction of diabetes by streptozotocin, an ROI-generating agent, was also attenuated by TRX overexpression in beta cells. This is the first direct demonstration that an antioxidative and antiapoptotic protein protects beta cells in vivo against both autoimmune and drug-induced diabetes. Our results strongly suggest that oxidative stress plays an essential role in the destruction of beta cells by infiltrating inflammatory cells in IDDM.

Animals↗
PubMed1998

Mistletoe lectin I forms a double trefoil structure.

The quaternary structure of mistletoe lectin I (MLI), a type II ribosome inactivating protein, has been determined by X-ray crystallography. A definitive molecular replacement solution was determined for MLI using the co-ordinates of the homologue ricin as a search model. MLI exists as an [AB]2 dimer with internal crystallographic two-fold symmetry. Domain I of the B chains is non-covalently associated through interactions involving three looped chains (alpha, beta, gamma) in each molecule of the dimer, forming a double trefoil structure. The ricin molecule which shares 52% sequence homology with MLI has a disulphide bridge between Cys20 and Cys39 in the alpha loop. An evolutionary mutation has replaced Cys39 with serine in MLI. This mutation appears to allow the alpha loop the flexibility required to take up its place at the dimer interface, and also suggests a rationale for why ricin does not form dimers. Measurement of retention times using FPLC gel filtration confirms that dimerisation also occurs in solution between MLI B chains with an association constant Ka = 10(6) M.

Amino Acid Sequence↗
PubMed1998

Accelerated formation of N epsilon-(carboxymethyl) lysine, an advanced glycation end product, by glyoxal and 3-deoxyglucosone in cultured rat sensory neurons.

The formation of advanced glycation end products (AGEs) is associated with pathophysiological changes with aging and disease processes. In the neurodegeneration in Alzheimer's disease and other neurodegenerative diseases. AGEs are speculated to play a role in their pathogenesis. We provide the first evidence for the induction of AGEs in cultured neuronal cells. Glyoxal and 3-deoxyglucosone (3-DG), AGE precursors, induced N epsilon-(carboxymethyl) lysine (CML), a well characterized and major AGE structure, in cultured rat sensory neurons in a time- and dose-dependent manner. CML formation was prevented by addition of aminoguanidine, an inhibitor of AGE formation. This culture system provides a useful model to analyze the role of the glycoxidation reaction in neuronal aging and neurodegenerative disorder.

Animals↗
PubMed1998

Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3.

The propagation of embryonic stem (ES) cells in an undifferentiated pluripotent state is dependent on leukemia inhibitory factor (LIF) or related cytokines. These factors act through receptor complexes containing the signal transducer gp130. The downstream mechanisms that lead to ES cell self-renewal have not been delineated, however. In this study, chimeric receptors were introduced into ES cells. Biochemical and functional studies of transfected cells demonstrated a requirement for engagement and activation of the latent trancription factor STAT3. Detailed mutational analyses unexpectedly revealed that the four STAT3 docking sites in gp130 are not functionally equivalent. The role of STAT3 was then investigated using the dominant interfering mutant, STAT3F. ES cells that expressed this molecule constitutively could not be isolated. An episomal supertransfection strategy was therefore used to enable the consequences of STAT3F expression to be examined. In addition, an inducible STAT3F transgene was generated. In both cases, expression of STAT3F in ES cells growing in the presence of LIF specifically abrogated self-renewal and promoted differentiation. These complementary approaches establish that STAT3 plays a central role in the maintenance of the pluripotential stem cell phenotype. This contrasts with the involvement of STAT3 in the induction of differentiation in somatic cell types. Cell type-specific interpretation of STAT3 activation thus appears to be pivotal to the diverse developmental effects of the LIF family of cytokines. Identification of STAT3 as a key transcriptional determinant of ES cell self-renewal represents a first step in the molecular characterization of pluripotency.

Animals↗