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T Nishikawa

Publications and source records attributed to T Nishikawa.

At least 163 records · Page 9Linked to original sources
PubMed2000

The missing link: a single unifying mechanism for diabetic complications.

A causal relationship between chronic hyperglycemia and diabetic microvascular disease, long inferred from various animal and clinical studies, has now been definitely established by data from the Diabetes Control and Complications Trial (DCCT), a multicenter, randomized, prospective, controlled clinical study. A relationship between chronic hyperglycemia and diabetic macrovascular disease in patients with non-insulin-dependent diabetes mellitus (NIDDM) is also supported by the Kumamoto study. How does hyperglycemia induce the functional and morphologic changes that define diabetic complications? Vascular endothelial cells are a major target of hyperglycemic damage, but the mechanisms underlying this damage remain incompletely understood. Three seemingly independent biochemical pathways are involved in the pathogenesis: glucose-induced activation of protein kinase C (PKC) isoforms: increased formation of glucose-derived advanced glycation end products; and increased glucose flux through the aldose reductase pathway. The relevance of each of these three pathways is supported by animal studies in which pathway-specific inhibitors prevent various hyperglycemia-induced abnormalities. Hyperglycemia increases reactive oxygen species (ROS) production inside cultured bovine aortic endothelial cells. In this paper, we show that ROS may activate aldose reductase, induce diacylglycerol, activate PKC, induce advanced glycation end product formation, and activate the pleiotropic transcription factor nuclear factor-kappa B (NF-kappaB). These data demonstrate that a single unifying mechanism of induction, increased production of ROS, serves as a causal link between elevated glucose and each of the three major pathways responsible for diabetic damage.

Animals↗
PubMed2000

Clinicopathologic study associated with long-term survival in Japanese patients with node-negative breast cancer.

This study was undertaken to determine the absolute and relative value of blood vessel invasion (BVI) using both factor VIII-related antigen and elastica van Gieson staining, proliferating cell nuclear antigen (PCNA), p53, c-erbB-2, and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including PCNA, p53, c-erbB-2 using permanent-section immunohistochemistry, clinical tumour size (T), histological grade (HG), mitotic index (MI), tumour necrosis (TN), lymphatic vessel invasion (LVI) and BVI, followed for a median of 10 years (range 1-20). Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that BVI, PCNA, T, HG, MI, p53, c-erbB-2 and LVI were significantly predictive of 20-year RFS or OS. Multivariate analysis showed that BVI (P = 0.0159, P = 0.0368), proliferating cell nuclear antigen (PCNA) (P = 0.0165, P = 0.0001), and T (P = 0.0190, P = 0.0399) were significantly independent prognostic factors for RFS or OS respectively. BVI, PCNA and T were independent prognostic indicators for RFS or OS in Japanese patients with node-negative breast cancer and are useful in selecting high-risk patients who may be eligible to receive strong adjuvant therapies.

Adolescent↗
PubMed2000

Neutrophilia associated with anaplastic carcinoma of the thyroid: production of macrophage colony-stimulating factor (M-CSF) and interleukin-6.

Cancers associated with marked neutrophilia are relatively rare. We report here two cases of anaplastic thyroid carcinoma associated with neutrophilia. We measured the concentrations of granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in sera, pleural effusion, cyst fluid of the thyroid carcinoma region, or culture supernatants of carcinoma cells. Maximum levels of elevated white blood cell counts reached 106.1 x 10(9)/L (neutrophils 103.0 x 10(9)/L) in case 1 and 62.3 x 10(9)/L (neutrophils 57.9 x 10(9)/L) in case 2. Acute-phase reactants were elevated to various degrees, and hypercalcemia was found in both cases. IL-6, G-CSF, and M-CSF seemed to play the principal roles in neutrophilia in case 1, and the elevated levels of IL-6 and M-CSF seemed to mainly contribute to neutrophilia in case 2. Immunohistochemical staining revealed that carcinoma cells themselves produce IL-6 regardless of the types of carcinoma cells. To our knowledge, this is the first report describing the contribution of M-CSF to neutrophilia in patients with thyroid carcinoma.

Adenocarcinoma, Papillary↗
PubMed2000

Prediction whether a human cDNA sequence contains initiation codon by combining statistical information and similarity with protein sequences.

MOTIVATION: In the previous works, we developed ATGpr, a computer program for predicting the fullness of a cDNA, i.e. whether it contains an initiation codon or not. Statistical information of short nucleotide fragments was fully exploited in the prediction algorithm. However, sequence similarities to known proteins, which are becoming increasingly available due to recent rapid growth of protein database, were not used in the prediction. In this work, we present a new prediction algorithm based on both statistical and similarity information, which provides better performance in sensitivity and specificity. RESULTS: We evaluated the accuracy of ATGpr for predicting fullness of cDNA sequences from human clustered ESTs of UniGene, and we obtained specificity, sensitivity, and correlation coefficient of this prediction. Specificity and sensitivity crossed at 46% over the ATGpr score threshold of 0.33 and the maximum correlation coefficient of 0.34 was obtained at this threshold. Without ATGpr we found it effective to use alignments with known proteins for predicting the fullness of cDNA sequences. That is, specificity increased monotonously as similarity (identity of the alignments) increased. Specificity was achieved greater than 80% if identity was greater than 40%. For more effective prediction of fullness of cDNA sequences we combined the similarity (identity of query sequence) with known proteins and ATGpr score. As a result, specificity became greater than 80% if identity was greater than 20%. AVAILABILITY: The prediction program, called ATGpr_ sim, is available at http://www.hri.co.jp/atgpr/ATGpr_sim.html CONTACT: nisikawa@crl.hitachi.co.jp

Amino Acid Sequence↗
PubMed2000

Evidence for GABA(A) receptor agonistic properties of ketamine: convulsive and anesthetic behavioral models in mice.

UNLABELLED: We examined the potentiation by ketamine of the gamma-aminobutyric acid(A) (GABA(A)) receptor function using convulsive and anesthetic behavioral models in adult male ddY mice. General anesthetic potencies were evaluated by a rating scale, which provided the data for anesthetic scores, loss of righting reflex, duration, and recovery time. All drugs were administered intraperitoneally. Small subanesthetic doses of ketamine did inhibit tonic seizures induced by a large dose of the GABA(A) receptor antagonist bicuculline (8 mg/kg). The 50% effective dose value was 15 (95% confidence limits 10-22) mg/kg. Even large anesthetic doses (100-150 mg/kg) did not suppress clonic seizures in 50% of the animals. The GABA(A) receptor agonist, muscimol (0.32-1.12 mg/kg), potentiated ketamine-induced anesthesia in a dose-dependent fashion (P < 0.05). Similarly, the benzodiazepine receptor agonist, diazepam (1-3 mg/kg), augmented ketamine anesthesia in a dose-dependent manner (P < 0.05). Bicuculline (2-5 mg/kg) dose-dependently antagonized ketamine-induced anesthesia (P < 0.05). Neither the benzodiazepine receptor antagonist, flumazenil (2-20 mg/kg), nor the GABA synthesis inhibitor, L-allylglycine (200 mg/kg), affected the anesthetic action of ketamine. These results suggest that ketamine has GABA(A) receptor agonistic properties and that ketamine-induced anesthesia is mediated, at least in part, by GABA(A) receptors. IMPLICATIONS: We examined the potentiation by ketamine of the gamma-aminobutyric acid(A) receptor function using convulsive and anesthetic behavioral models in mice. Subanesthetic doses of ketamine-inhibited tonic convulsions induced by the gamma-aminobutyric acid(A) receptor antagonist bicuculline. The gamma-aminobutyric acid(A) receptor agonist, muscimol, potentiated ketamine-induced anesthesia. Bicuculline antagonized ketamine anesthesia, but the benzodiazepine receptor antagonist, flumazenil, and the gamma-aminobutyric acid synthesis inhibitor, L-allyglycine, did not. The effects of ketamine on the gamma-aminobutyric acid(A) receptors appear to correlate with its anesthetic actions.

Allylglycine↗
PubMed2000

Evaluating hemodynamic and T wave criteria of simulated intravascular test doses using bupivacaine or isoproterenol in anesthetized children.

UNLABELLED: An increase in T wave amplitude > or =25% is a reliable indicator for detecting intravascular injection of lidocaine-epinephrine test dose in anesthetized children. We examined whether a simulated IV test dose containing bupivacaine instead of lidocaine, and isoproterenol instead of epinephrine, produces reliable changes in heart rate (HR) and T wave morphology. One hundred healthy infants and children (6-72 mo) were randomized to one of five groups (n = 20 each) during 1.0 minimum alveolar anesthetic concentration sevoflurane and 67% nitrous oxide in oxygen: atropine pretreatment (0.01 mg/kg IV) followed by 0.25% bupivacaine containing epinephrine 0.5 microg/kg IV, atropine followed by normal saline, atropine followed by 1% lidocaine containing isoproterenol 0.1 microg/kg, saline pretreatment followed by the lidocaine-isoproterenol test dose, and saline followed by saline. HR was recorded every 20 s and T wave amplitude of lead II was continuously recorded. All patients receiving the bupivacaine-epinephrine test dose and none receiving saline met the HR (positive if > or =10 bpm increase) and T wave criteria (positive if > or =25% increase in amplitude). The isoproterenol-containing test dose produced positive responses based only on the HR criterion with or without atropine pretreatment. Our results indicate that HR and T wave changes are useful if a bupivacaine-epinephrine test dose is used and that HR is the only useful indicator if an isoproterenol-containing test dose is used in sevoflurane-anesthetized children. IMPLICATIONS: To determine if an epidurally administered local anesthetic has been unintentionally injected into a blood vessel, a small dose of epinephrine or isoproterenol may be added to a local anesthetic. We found that an increase in heart rate > or =10 bpm and an increase in T wave amplitude of lead II >or =25% are useful indicators for detecting accidental intravascular injection of an epinephrine-containing test dose in sevoflurane-anesthetized children, whereas only a heart rate change is a reliable diagnostic tool if an isoproterenol-containing test dose is used.

Adrenergic beta-Agonists↗
PubMed2000

Aging reduces the efficacy of the simulated epidural test dose in anesthetized adults.

UNLABELLED: Aging is associated with reduced beta-adrenergic responsiveness. However, the age-related effects on hemodynamic changes and effectiveness of a simulated epidural IV test dose have not been defined during general anesthesia. We studied 20 (140 total) consecutive patients (ASA physical status I) assigned in each of the following age groups after endotracheal intubation and during stable end-tidal sevoflurane 2% and 67% nitrous oxide anesthesia (in yr): 10s, 20s, 30s, 40s, 50s, 60s, and 70s. Each group first received normal saline 3 mL IV, followed 4 min later by 1.5% lidocaine 3 mL plus 15 microg epinephrine (1:200,000) IV for 5 s. Heart rate (HR) and systolic blood pressure (SBP) were continuously monitored for 4 min after saline administration and the test dose injections. None receiving IV saline and all patients receiving IV test dose in age groups 10s to 50s developed HR increases > or = 10 bpm, whereas 17 and 13 patients met this HR criterion in age groups 60s and 70s (85% and 65% sensitivities), respectively. There was a significant inverse correlation between the maximum HR increase and the age (P: < 0.001 by Spearman's rank correlation). However, none receiving saline and all patients receiving IV test dose in all age groups developed SBP increases of 15 mm Hg, resulting in 100% efficacy based on the SBP criterion. We conclude that during stable sevoflurane anesthesia administration (a) the efficacy based on the HR criterion for detecting accidental intravascular injection of the epidural test dose is age-dependent, (b) the HR criterion may be clinically applicable only in patients <60 yr of age, and (c) the SBP criterion is effective for all age groups studied. IMPLICATIONS: To determine whether an epidurally administered local anesthetic has been unintentionally injected into a blood vessel, a small dose of epinephrine is often added to a local anesthetic. We found that an increase in systolic blood pressure > or = 15 mm Hg is a more useful indicator than an increase in heart rate > or = 10 bpm in the patients > or = 60 yr old during stable sevoflurane anesthesia administration.

Adolescent↗
PubMed2000

The efficacy of hemodynamic and T wave criteria for detecting intravascular injection of epinephrine test doses in anesthetized adults: a dose-response study.

UNLABELLED: Recent studies have shown that an epidural test dose containing 15 microg of epinephrine has a sensitivity and specificity of 100% for detecting intravascular injection based on the systolic blood pressure (SBP) (positive if > or =15-mm Hg increase) and the T wave criteria (positive if > or =0.1 mV and 25% decrease in amplitude), whereas the modified heart rate (HR) criterion (positive if > or =10-bpm increase) produced uncertain results in sevoflurane-anesthetized adults. Because a fractional dose of the test dose may be injected intravascularly in actual clinical situations, we designed this study to determine, in a dose-related manner, the efficacy and minimum effective dose of epinephrine based on those hemodynamic and the T wave criteria. Eighty healthy adult patients were randomly assigned to one of four groups according to a simulated IV test dose under 2% end-tidal sevoflurane and nitrous oxide anesthesia after endotracheal intubation (n = 20 each). The saline group received 3 mL of normal saline IV; the epinephrine-15 group received 3 mL of 1.5% lidocaine containing 15 microg of epinephrine (1); and the epinephrine-10 and -5 groups received 2 and 1 mL of the test dose of the identical components, respectively. HR, SBP, and lead II of the electrocardiograph were recorded continuously for 5 min after the IV injection of the study drug. Sensitivities and specificities of 100% were obtained based on the HR and the SBP criteria only if 15 microg of epinephrine was injected IV, whereas sensitivities and specificities of 100% were obtained based on both T wave criteria after 15 and 10 microg of epinephrine was injected IV. Two blinded observers were able to detect all T wave changes in patients who received 15, 10, and 5 microg of epinephrine IV, resulting in 100% efficacy (P: < 0.05 versus HR and SBP criteria). We conclude that minimum effective epinephrine doses for detecting accidental intravascular injection are 15 microg on the HR and the SBP criteria, and 10 microg on both T wave criteria, and that observing T wave changes may detect even smaller (5 microg) doses of epinephrine injected IV in adult patients anesthetized with sevoflurane and nitrous oxide. IMPLICATIONS: To determine whether an epidural catheter is in a blood vessel, an epidural test dose containing 15 microg of epinephrine is used. We found that a decrease in T wave amplitude appears to be more sensitive than heart rate and systolic blood pressure change for detecting accidental intravascular injection of a small dose of epinephrine-containing test dose in sevoflurane-anesthetized patients.

Adult↗
PubMed2000

Reevaluation of rectal ketamine premedication in children: comparison with rectal midazolam.

BACKGROUND: Results of previous studies of rectal ketamine as a pediatric premedication are clouded because of lack of dose-response relation, inappropriate time of assessing sedative effects, and previous administration or coadministration of benzodiazepines. Therefore, the authors reevaluated the efficacy of rectally administered ketamine in comparison with 1 mg/kg rectal midazolam. METHODS: Sixty-six infants and children (age, 7-61 months) who were American Society of Anesthesiologists physical status I and who were undergoing minor surgeries as in-patients were randomized to receive 5 mg/kg ketamine (n = 16), 7 mg/kg ketamine (n = 16), 10 mg/kg ketamine (n = 17), or 1 mg/kg midazolam (n = 17) via rectum. A blinded observer scored sedation 45 min and 15 min after administration of ketamine and midazolam, respectively, when children were separated from parent(s) for inhalational induction. All children underwent standardized general anesthesia with sevoflurane, nitrous oxide, and oxygen with endotracheal intubation. Blood pressure, heart rate, and oxyhemoglobin saturation were determined before, during, and after anesthesia. Postoperative recovery characteristics and incidence of adverse reactions were also assessed. RESULTS: Most children (88%) who received rectally 10 mg/kg ketamine or 1 mg/kg midazolam separated easily from their parents compared with those (31%) who received 7 or 5 mg/kg rectal ketamine (P < 0.05). Similarly, more children who received 10 mg/kg ketamine or 1 mg/kg midazolam underwent mask induction without struggling or crying compared with those who received 7 or 5 mg/kg ketamine (P < 0.05). There were no clinically significant changes in blood pressure, heart rate, and oxyhemoglobin saturation after administration of either drug. Immediately after surgery, more children receiving midazolam or 5 mg/kg ketamine were agitated compared with 7 or 10 mg/kg ketamine. Ketamine, 7 and 10 mg/kg, provided postoperative analgesia, but the largest dose of ketamine was associated with delayed emergence from general anesthesia. CONCLUSIONS: The results indicate that rectally administered ketamine alone produces dose-dependent sedative effects in children, when evaluated at its predicted peak plasma concentration. Ketamine, 10 mg/kg, has a delayed onset but is as effective as 1 mg/kg midazolam for sedating healthy children before general anesthesia. However, 10 mg/kg rectal ketamine is not recommended for brief surgeries because of prolonged postoperative sedation.

Adjuvants, Anesthesia↗
PubMed2000

Significance of tau phosphorylation and protein kinase regulation in the pathogenesis of Alzheimer disease.

The role of the phosphatidylinositol-3 kinase pathway in the hyperphosphorylation of tau protein was investigated in cultured cells. Human kidney 293T-cells were cotransfected with tau and glycogen synthase kinase-3 (GSK-3) genes or tau and protein kinase B genes. The phosphorylation of tau protein was increased by cotransfection with GSK-3; however, it was decreased by cotransfection with protein kinase B. Human neuroblastoma SY5Y cells were treated with wortmannin, an inhibitor of phosphatidylinositol-3 kinase, and only transient (after 1 hour) activation of GSK-3 and hyperphosphorylation of tau protein were observed. However, continuous inactivation of protein kinase B was observed, suggesting the involvement of protein kinases other than protein kinase B in the phosphorylation and inactivation of GSK-3 after 3 hours. In cells treated with wortmannin, protein kinase C delta fragments were observed, and the protein kinase C activity increased after 3 hours, whereas treatment of cells with z-DEVD-fmk, an inhibitor of caspase-3, inhibited fragmentation of protein kinase C delta and induced continuous activation of GSK-3. It is suggested that fragmentation of protein kinase C delta during the process of apoptosis results in the phosphorylation and the inactivation of GSK-3. Those data suggest that, in Alzheimer disease, more complicated mechanisms are involved in the process of phosphorylation of tau protein predominantly regulated by P13K pathway.

Alzheimer Disease↗
PubMed2000

Primary bone tumors of the femur presenting with spinal symptoms: a report of two cases and review of the literature.

Two case reports of femoral bone lesions simulating lumbar spinal disease are presented. Physical examination and case history were strongly suggestive of lumbar spinal pathology. In case 1, surgical resection of a venous hemangioma in the lumbar epidural space was performed but did not relieve pain. In case 2, conservative treatments for a protruded disk were performed for 3 months before an accurate diagnosis was made. After correct diagnoses were made, excision of the femoral tumors brought rapid relief of all abnormal findings in both cases. Compared with other causes of sciatica, femoral bone tumors are rare. However, careful attention should be paid to rule out these lesions if the diagnosis of a lumbar spinal disease is uncertain. Bone scintigraphy seems to be a sensitive diagnostic method to detect extraspinal osseous lesions.

Adult↗
PubMed2000

Cardiovascular response and stress reaction to flumazenil injection in patients under infusion with midazolam.

OBJECTIVES: To evaluate the cardiovascular response and acute stress reaction after arousal induced by a benzodiazepine antagonist, flumazenil, in patients sedated with midazolam. DESIGN: Prospective study. SETTING: Emergency center in a university hospital. PATIENTS: A total of 12 patients were ventilated mechanically under sedation with midazolam. INTERVENTIONS: We monitored the consciousness level, heart rate, systemic blood pressure, pulmonary artery pressure, and pulmonary artery occlusion pressure before and after a bolus injection of 0.5 mg of flumazenil. The score for the consciousness level represents the sum of the scores for eye opening and best motor response, as determined by the Glasgow Coma Scale. We measured the cardiac output, concentrations of norepinephrine, epinephrine, and 3-methoxy-4-hydroxyphenylethyleneglycol in plasma, and concentration of cortisol in serum. We calculated the left ventricular ejection fraction, cardiac index, systemic vascular resistance index, pressure-rate product, systemic oxygen delivery, and systemic oxygen consumption at 0, 10, 30, and 60 mins after injection of flumazenil. MEASUREMENTS AND MAIN RESULTS: The serum benzodiazepine's receptor binding activity in serum was in the range from 50 to 1000 ng/mL before injection of flumazenil. Flumazenil improved the consciousness level from 6.7+/-2.0 to 8.9+/-1.6 and induced transient elevations in heart rate, blood pressure, systolic pulmonary artery pressure, and pulmonary artery occlusion pressure. Left ventricular ejection fraction, oxygen delivery index, and pressure-rate product increased significantly, from 61%+/-8%, 640+/-170 mL/min/m2, and 13,300+/-2600 mm Hg/min at 0 mins to 67% +/-5%, 710+/-220 mL/min/m2, and 16,500+/-4400 mm Hg/min at 10 mins, respectively. Concentrations of norepinephrine and epinephrine in plasma increased significantly, from 890+/-840 pg/mL and 220+/-360 pg/mL, respectively, at 0 mins to 990+/-850 pg/mL and 270+/-300 pg/mL, respectively, at 10 mins. There were no significant changes in the plasma concentration of 3-methoxy-4-hydroxyphenylethyleneglycol, the serum concentration of cortisol after the administration of flumazenil. CONCLUSIONS: Flumazenil did not result in a significant acute stress reaction in midazolam-sedated patients, but it increased myocardial oxygen consumption by enhancing sympathetic nervous activity or antagonizing cardiovascular depression induced by midazolam.

Acute Disease↗
PubMed2000

Use of autoantigen-knockout mice in developing an active autoimmune disease model for pemphigus.

The development of experimental models of active autoimmune diseases can be difficult due to tolerance of autoantigens, but knockout mice, which fail to acquire tolerance to the defective gene product, provide a useful tool for this purpose. Using knockout mice lacking desmoglein 3 (Dsg3), the target antigen of pemphigus vulgaris (PV), we have generated an active disease model for this autoantibody-mediated disease. Dsg3(-/-) mice, but not Dsg3(+/-) littermates, produced anti-Dsg3 IgG that binds native Dsg3, when immunized with recombinant mouse Dsg3. Splenocytes from the immunized Dsg3(-/-) mice were then adoptively transferred into Rag-2(-/-) immunodeficient mice expressing Dsg3. Anti-Dsg3 IgG was stably produced in the recipient mice for more than 6 months without further boosting. This IgG bound to Dsg3 in vivo and disrupted the cell-cell adhesion of keratinocytes. Consequently, the recipient mice developed erosions in their oral mucous membranes with typical histologic findings of PV. In addition, the recipient mice showed telogen hair loss, as found in Dsg3(-/-) mice. Collectively, the recipient mice developed the phenotype of PV due to the pathogenic anti-Dsg3 IgG. This model will be valuable for developing novel therapeutic strategies. Furthermore, our approach can be applied broadly for the development of various autoimmune disease models.

Animals↗
PubMed2000

Behavior of smooth muscle cells during arterial ductal closure at birth.

To determine which part of the smooth muscle cells (SMCs) of the ductus arteriosus (DA) contribute to duct closure after birth, we looked for areas in which SM2 myosin heavy chain (MHC) mRNA expression, which is associated with contraction of smooth muscle, and apoptosis could be detected in the DA during development. In situ hybridization revealed that the SM2 MHC mRNA was strongly positive in the longitudinally oriented SMCs and inner layer of the circularly oriented SMCs just before birth. Apoptotic cells were detected in the SMCs of the DA from 1 day after birth. Histochemical analysis using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) revealed significant numbers of TUNEL-positive nuclei in the longitudinally oriented SMCs and the inner layer of the circularly oriented SMCs. Masson-stained sections showed that the TUNEL-positive area in the DA was replaced by connective tissue from 1 day after birth. These results suggest that the increase in the SM2 MHC mRNA expression and the induction of apoptosis are present at the same site in the media of the DA. Therefore, the SMCs in this area may play an important role in duct constriction and remodeling of the vessel wall after birth.

Animals↗
PubMed2000

[Understanding of molecular pathogenesis of Alzheimer's disease: implications for drug development].

Recent advances in the knowledge about Alzheimer pathogenesis indicate several tactics for the development of drugs to treat Alzheimer's disease. Firstly, the function of presenilin, the causative gene for most familial Alzheimer's disease, has been demonstrated to be the protease in the Notch signaling system. Presenilin cleaves the transmembrane domain of the C-terminal fragment of the Notch-1 molecule, which is generated by proteolysis by furin-like proteases. APP is also cleaved by presenilin at the gamma cut site, implying that presenilin is gamma-secretase itself or at least closely functioning with gamma-secretase. A recent paper has demonstrated that immunization of APP transgenic mouse with amyloid beta 42 may decrease and prevent amyloid deposition in brain tissue. This unique and novel approach may open the new tactics for developing anti-dementia drugs. Another important finding comes from the identification of the function of prolyl isomerase. It is demonstrated that pin 1, intra-nuclear prolyl isomerase, can restore the microtubule binding capacity of phosphorylated tau, which clearly shows a solid strategy for developing drugs for preventing neuronal degeneration.

Alzheimer Disease↗
PubMed2000

Formate dehydrogenase gene of Arabidopsis thaliana is induced by formaldehyde and not by formic acid.

Variability of expression of formate dehydrogenase (FDH) caused by uptake of C-1 compounds was examined by using Arabidopsis thaliana as a model plant. Effects of uptake of several C-1 compounds were evaluated by Northern blot analysis using cDNA of A. thaliana FDH prepared by cloning on the basis of known sequence. As a result, expression of the FDH gene in A. thaliana was not intensely influenced by formic acid, an inherent substrate for FDH, but strongly induced by its reduced form, formaldehyde.

Journal Article↗