Search PubMed⌕ Search

Biomedical subjects

K Okamoto

Publications and source records attributed to K Okamoto.

At least 253 records · Page 14Linked to original sources
PubMed2000

Properties and actions of heat-stable enterotoxin of Escherichia coli.

The heat-stable enterotoxins (STs) produced by enterotoxigenic Escherichia coli are classified into two groups, methanol-soluble (STI) and methanol-insoluble (STII) enterotoxins. These are distinct toxins with unique properties. Their features in common include heat-stability, low molecular weight, secretion from the bacteria, and ability to induce fluid secretion from the intestine. STI is an 18- or 19-amino acid extracellular peptide with three intramolecular disulfide bonds, which is produced by proteolytic cleavage of 72 amino acid precursor. The STI in the lumen of the intestine binds to specific protein receptors (guanylate cyclase C) located in the brush border membrane and leads to elevation of intracellular cyclic GMP level. Several factors involved in the activation of guanylate cyclase by STI have been identified. Elevation of cyclic GMP level induces intestinal fluid secretion by stimulation of chloride secretion. Cystic fibrosis transmembrane conductance regulator, which is a chloride channel, might be involved in chloride secretion. In contrast, STII is a 48-amino acid peptide with two intramolecular disulfide bonds, which results from 71 amino acid precursor. Compared with STI, the steps that lead to intestinal fluid secretion by STII are not well established. It has been proposed that sulfatide in the brush border is a receptor for STII and that the STII bound to the receptor opens GTP-binding regulatory protein-linked calcium channels. These actions of STII induce not only stimulation of the production of secretagogues such as prostaglandin E2 and serotonin, but also activation of the calcium-calmodulin-dependent protein kinase II in the cells.

Animals↗
PubMed2000

[Glioblastoma with a marked elevation of total protein and albumin in the cerebrospinal fluid].

We describe a patient with glioblastoma who showed very high levels of total protein and albumin in the cerebrospinal fluid. The patient was a 57-year-old man who underwent subtotal removal of a glioblastoma from the left temporal lobe. Two weeks after the operation, he had quadriplegia and a lumbar puncture was performed. The concentrations of total protein and albumin in the cerebrospinal fluid were 6000 mg/dl and 3600 mg/dl, respectively, which were more than 100 times higher than the upper limits of the reference ranges and were close to their serum levels. The magnetic resonance image suggested that these abnormal values were due to total spinal cord dissemination of the tumor. The results of the cerebrospinal fluid examination showed that the albumin concentration in the fluid might increase to the serum level and the prozone phenomenon should be kept in mind when measuring its concentration in the fluid.

Albumins↗
PubMed2000

Prevention of lymphocyst formation following systematic lymphadenectomy.

BACKGROUND: The occurrence of pelvic lymphocysts is an important complication following systematic lymphadenectomy for gynecological malignancies. We employed a procedure to prevent vaginal shortening following radical hysterectomy and we examined whether this procedure could be effective in preventing pelvic lymphocyst formation. METHODS: We studied the incidence of lymphocysts in 190 patients with 84 cervical cancers, 74 endometrial cancers and 32 ovarian cancers, using computed tomographic examination at 3 and 6 months subsequent to the surgery. The surgery included radical hysterectomy and a procedure to prevent vaginal shortening (101), modified radical hysterectomy (79) and simple hysterectomy (7), with systematic lymphadenectomy. RESULTS: There was a significant difference in the incidence of pelvic lymphocysts between cervical cancer (4.8%) and ovarian cancer (18.8%). The postoperative incidence of lymphocyst formation in patients undergoing radical hysterectomy with the procedure to prevent vaginal shortening (5.9%) was significantly lower than in those who underwent modified radical hysterectomy (15.2%). CONCLUSION: Our procedure to prevent vaginal shortening could be effective in preventing not only the shortening of the vagina but also the occurrence of pelvic lymphocysts in patients undergoing radical hysterectomy with systematic lymphadenectomy for gynecological malignancies.

Adolescent↗
PubMed2000

Combination of inhaled nitric oxide therapy and inverse ratio ventilation in patients with sepsis-associated acute respiratory distress syndrome.

Inverse ratio ventilation (IRV) is a ventilatory technique that uses an inspiratory to expiratory ratio (I:E) greater than 1:1. We studied the effects of mechanical ventilation with an I:E of 1:3, 1:1, and 2:1 on arterial oxygenation in 10 patients with sepsis-associated acute respiratory distress syndrome (ARDS). At each I:E, patients received 0 and 4 ppm of inhaled nitric oxide (INO) in random order for 30 min. Respiratory and cardiovascular parameters were measured. Of the 10 patients studied, 7 responded to IRV and 3 did not. An increase in the I:E and the addition of INO significantly improved arterial oxygenation in the responders (p < 0. 0001 and p < 0.006, respectively). The combination of an increase in the I:E and INO had an additive effect on arterial oxygenation. The combined use of IRV and INO is a more effective method of avoiding hypoxemia than either INO or IRV alone.

Administration, Inhalation↗
PubMed2000

Effects of recombinant tissue-type plasminogen activator on life-threatening acute pulmonary thromboembolism in a canine model: a comparative study of e6010 and alteplase.

We compared the effects a novel recombinant tissue-type plasminogen activator (rt-PA) E6010 with the more conventional therapeutic agent alteplase in a new canine model of life-threatening acute pulmonary thromboembolism (APTE). Fifty milliliters of autologous blood was obtained from anesthetized, adult mongrel dogs and mixed with 10,000 units of thrombin. The left pulmonary artery, pulmonary vein, and bronchus were ligated, and previously prepared blood clots were injected via the femoral vein until the mean pulmonary artery pressure (mPA) increased to 2.5-3.0 times over baseline mPA (control). E6010 (0.4 mg/kg) or alteplase (1.33 mg/kg) was administered to other animals following inducement of APTE. In control animals, 60 min after embolization, mPA increased from 13+/-3 mm Hg to 31+/-3 mm Hg (p < 0.0001), cardiac output (CO) decreased from 1.47+/-0.35 l/min to 1.15+/-0.39 l/min (p < 0.0001), and PaO2 decreased from 101+/-31 mm Hg to 65+/-20 mm Hg (p < 0.001). E6010 significantly reduced mPA from 31+/-3 mm Hg to 25+/-4 mm Hg (p < 0.0001) 30 min after administration. In the alteplase group, however, mPA did not significantly change. At 180 min following drug administration, further reduction of mPA was significantly observed in both treatments. CO and PaO2 did not improve after either treatment. The present study indicated that E6010 more rapidly reduced pulmonary hypertension in our APTE model. Because of its rapid action, E6010 might be a promising thrombolytic agent for treatment of APTE.

Acute Disease↗
PubMed1999

The expression of proinflammatory cytokine mRNA in the sciatic-tibial nerve of ischemia-reperfusion injury.

We evaluated the proinflammatory cytokines, TNF-alpha and IL-1beta, mRNA expression in the rat sciatic and tibial nerves following ischemia-reperfusion (IR) injury, using competitive RT-PCR, to explore the role of cytokines in IR injury. The expressions of both TNF-alpha and IL-1beta mRNA were related to severity of ischemia and occurred with reperfusion rather than ischemia alone. TNF-alpha gene expression peaked at 24 h of reperfusion, while that of IL-1beta peaked at 12 h. These data support the notion that the proinflammatory cytokines TNF-alpha and IL-1beta are involved in the inflammatory response of IR injury to the peripheral nervous system and may be involved in the pathophysiology of ischemic fiber degeneration.

Animals↗
PubMed1999

A role of cyclin G in the process of apoptosis.

Cyclin G was previously identified as a target gene of the p53 tumor suppresser protein, and levels of cyclin G are increased after induction of p53 by DNA damage. However, the function of cyclin G has not been established. To determine the effect of increased expression of cyclin G, retroviruses encoding cyclin G were constructed and used to infect three different murine cell lines. Cyclin G protein levels induced by the retroviruses were within the range seen after DNA damage induction of p53. In each case we observed that such over-expression of cyclin G augments the apoptotic process. TNF-alpha induction of apoptosis is increased by expression of cyclin G in NIH3T3 fibroblasts which express p53, as well as in 10.1 fibroblasts which contain no p53 allele. Additionally, we observed that while cyclin G expression is markedly reduced upon aggregate formation in embryonic carcinoma P19 cells, retrovirus-mediated over-expression of cyclin G enhances apoptotic cell death in aggregated P19 cells, and increases the extent of apoptosis caused by retinoic acid or serum starvation of these cells. These data demonstrate that cyclin G plays a facilitating role in modulating apoptosis induced by different stimuli. Moreover, we have discovered that cyclin G expression is rapidly induced in P19 cells after exposure to Bone Morphogenic Protein-4 (BMP-4), suggesting that cyclin G may mediate apoptotic signals generated by BMP-4.

3T3 Cells↗
PubMed1999

Hemolysin of Aeromonas sobria stimulates production of cyclic AMP by cultured cells.

Hemolysin of Aeromonas sobria possesses both cytotoxic activity against mammalian cells and enterotoxic activity. Histopathological examination revealed that hemolysin causes diarrhea without damaging the intestinal epithelial cells. And the fluid accumulated in the mouse intestinal loop by the action of the hemolysin is watery. These observations indicated that the enterotoxic activity of hemolysin is not dependent on its cytotoxic activity. To clarify the mechanism of the enterotoxic action of hemolysin, we examined cyclic nucleotide levels in cultured cells exposed to this toxin. These results showed that hemolysin stimulates the production of cyclic AMP in cultured cells and the cyclic AMPs thus produced emerge in the milieu of cells.

Aeromonas↗
PubMed1999

Dopamine and DOPA cause release of iron from ferritin and lipid peroxidation of liposomes.

We investigated dopamine (DA)- and DOPA-related release of iron from ferritin, and lipid peroxidation of liposomes induced by the released iron. Iron release increased with increasing DA or DOPA concentrations. Effects of SOD and an oxygen-reduced environment indicated that superoxide was partly responsible for iron release. The released iron induced lipid peroxidation at relatively low concentrations of DA or DOPA, while at high concentrations, peroxidation was inhibited. These findings indicate that the risk of lipid peroxidation depends on the DA/iron or DOPA/iron ratio even if the iron concentration is low. Our findings suggest that DA-containing neurons are always at risk of oxidative damage. Furthermore, DOPA therapy may modify the nigral degeneration by reducing or accelerating ferritin iron-dependent lipid peroxidation.

Animals↗
PubMed1999

Genetic analyses of proteolysis, hemoglobin binding, and hemagglutination of Porphyromonas gingivalis. Construction of mutants with a combination of rgpA, rgpB, kgp, and hagA.

Porphyromonas gingivalis produces arginine-specific cysteine proteinase (Arg-gingipain, RGP) and lysine-specific cysteine proteinase (Lys-gingipain, KGP) in the extracellular and cell-associated forms. Two separate genes (rgpA and rgpB) and a single gene (kgp) have been found to encode RGP and KGP, respectively. We constructed rgpA rgpB kgp triple mutants by homologous recombination with cloned rgp and kgp DNA interrupted by drug resistance gene markers. The triple mutants showed no RGP or KGP activity in either cell extracts or culture supernatants. The culture supernatants of the triple mutants grown in a rich medium had no proteolytic activity toward bovine serum albumin or gelatin derived from human type I collagen. Moreover, the mutants did not grow in a defined medium containing bovine serum albumin as the sole carbon/energy source. These results indicate that the proteolytic activity of P. gingivalis toward bovine serum albumin and gelatin derived from human type I collagen appears to be attributable to RGP and KGP. The hemagglutinin gene hagA of P. gingivalis possesses the adhesin domain regions responsible for hemagglutination and hemoglobin binding that are also located in the C-terminal regions of rgpA and kgp. A rgpA kgp hagA triple mutant constructed in this study exhibited no hemagglutination using sheep erythrocytes or hemoglobin binding activity, as determined by a solid-phase binding assay with horseradish peroxidase-conjugated human hemoglobin, indicating that the adhesin domains seem to be particularly important for P. gingivalis cells to agglutinate erythrocytes and bind hemoglobin, leading to heme acquisition.

Adhesins, Bacterial↗
PubMed1999

Apolipoprotein E4 accelerates dementia and increases cerebrospinal fluid tau levels in Alzheimer's disease.

To examine the effect of apolipoprotein E (ApoE) 4 on the progression of Alzheimer's disease (AD), the clinical course of 33 AD patients (17 cases with ApoE epsilon4 and 16 cases without ApoE epsilon4) was evaluated with the mini-mental state examination (MMSE) and cerebrospinal fluid (CSF) biological markers. The decline of MMSE scores to zero was shortened in the ApoE4 group. During a mean follow-up of 20 months, a significant increase of CSF tau levels was observed in the ApoE4 group. A lower level of CSF A beta1-42(43) was found in both the ApoE4 and non-ApoE4 groups than in age-matched normal controls. The ApoE epsilon4 allele accelerates the progression of dementia and increases the levels of CSF tau in AD patients.

Aged↗
PubMed1999

Redox-dependent regulation of nuclear import of the glucocorticoid receptor.

A number of transcription factors including the glucocorticoid receptor (GR) are regulated in a redox-dependent fashion. We have previously reported that the functional activity of the GR is suppressed under oxidative conditions and restored in the presence of reducing reagents. In the present study, we have used a chimeric human GR fused to the Aequorea green fluorescent protein and demonstrated that both ligand-dependent and -independent nuclear translocation of the GR is impaired under oxidative conditions in living cells. Substitution of Cys-481 for Ser within NL1 of the human GR resulted in reduction of sensitivity to oxidative treatment, strongly indicating that Cys-481 is one of the target amino acids for redox regulation of the receptor. Taken together, we may conclude that redox-dependent regulation of nuclear translocation of the GR constitutes an important mechanism for modulation of glucocorticoid-dependent signal transduction.

Amino Acid Sequence↗
PubMed1999

Inositol-1,4,5-trisphosphate accumulation induced by urinary pheromones in female rat vomeronasal epithelium.

The mechanisms involved in pheromone-induced responses in the vomeronasal neurons, especially in mammals, are still unclear. In the present study, we examined the effects of rat urine samples containing various types of pheromones regulating gonadal functions on the accumulation of cAMP and inositol 1,4,5-trisphosphate (IP3) in a vomeronasal membrane preparation from the female Wistar rat. Stimulation of the preparation with forskolin induced cAMP accumulation, but stimulation with urine samples excreted from the male Wistar rat, the female Wistar rat, and the male Donryu rat did not change cAMP levels. These results were consistent with the electrophysiological results showing that dialysis of a high concentration of cAMP into the vomeronasal neuron does not induce currents. Stimulation with the three urine samples induced the accumulation of IP3 in the membrane preparation. These results are consistent with previous electrophysiological results [K. Inamura, M. Kashiwayanagi, K. Kurihara, Inositol-1,4,5-trisphosphate induces responses in receptor neurons in rat vomeronasal sensory slices, Chem. Senses 22 (1997) 93-103; K. Inamura, M. Kashiwayanagi, K. Kurihara, Blockage of urinary responses by inhibitors for IP3-mediated pathway in rat vomeronasal sensory neurons, Neurosci. Lett. 233 (1997) 129-132]. After the treatment with Pertussis toxin (PTX), the male Wistar urine did not induce IP3 accumulation significantly. Application of the male Wistar urine decreased ADP-ribosylation of Gi with PTX, while that of the male Donryu urine decreased ADP-ribosylation of Go. Thus, the present results support a mechanism by which the responses of the rat vomeronasal neurons to urinary pheromones are mediated by IP3, Gi and/or Go.

Animals↗
PubMed1999

Carboxyl-terminal fragments of presenilin-1 are closely related to cytoskeletal abnormalities in Alzheimer's brains.

To clarify the role of presenilin-1 (PS-1) in the pathology of Alzheimer's disease (AD), we tested four antisera to PS-1. The specific antisera to the N-terminus (HSN-2) and C-terminus (HS-C) of PS-1 detected a 44/40kD holoprotein, a 25kD N-terminal fragment (NTF) and a 16kD C-terminal fragment (CTF) of PS-1 in COS-7 cells. The 25kD NTF and 16kD CTF were observed in human brains, and their amounts were not significantly different between the control and AD brains. The antibody HS-C labeled extensive neurofibrillary tangles, dystrophic neurites and curly fibers in the AD brains. In the paired helical filament (PHF) fraction containing A68 protein from AD brains, a smear pattern of CTFs was revealed. Antisera (HS-L292 and HS-L300) to cleavage sites of PS-1 also revealed immunoreactive neurofibrillary tangles in the AD brain sections and the smear pattern of CTFs of A68 protein fraction. The CTFs of PS-1 accumulate with PHF tau, suggesting a close relationship between PS-1 and cytoskeletal abnormalities in AD brains.

Aged↗