Biomedical subjects

S Takeuchi

Publications and source records attributed to S Takeuchi.

At least 91 records · Page 5Linked to original sources

PubMed2001

Effect of bacterial metabolism in the intestine on colorectal tumors induced by 1,2-dimethylhydrazine in transgenic mice harboring human prototype c-Ha-ras genes.

The number of colorectal tumors per mouse induced by 1,2-dimethylhydrazine in transgenic (Tg) mice carrying human c-Ha-ras genes was significantly reduced by ingestion of apple pectin (AP) or a culture condensate of Bifidobacterium longum(MB) compared with a control diet and non-Tg mice. However, there were no differences in the composition of fecal flora, water content, beta-glucuronidase and beta-glucosidase activities, and concentrations of organic acids and putrefactive products in the feces between the AP or MB diet and the control diet, or between the Tg mice and non-Tg mice. The concentration of secondary bile acids in the MB diet group was higher than that in the control group. These results suggested that there was no relationship between prevention of colorectal tumors in Tg mice and the AP or MB diet, or improvement of the intestinal environment due to these functional foods.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2001

[Long-term results of vitrectomy for complications of proliferative diabetic retinopathy].

PURPOSE: To evaluate the long-term results of vitrectomy for complications of proliferative diabetic retinopathy. METHODS: Five-year follow-up examinations were obtained on 33 eyes of 24 patients that underwent vitrectomy. The preoperative status of macula was no detachment(group 1, 9 eyes), macular detachment(group 2, 17 eyes), and traction macular fold (group 3, 7 eyes). RESULTS: The retina was successfully reattached in 17 eyes(100%). The final visual acuity obtained was as follows: 75% of the eyes had acuity of 0.1 or better in group 1, 65% in group 2, and 86% in group 3; 44% had acuity of 0.5 or better in group 1, 24% in group 2, and 14% in group 3; and 11% had acuity of 0.05 or worse in group 1, 18% in group 2, and 0% in group 3. 11% of the final visual acuity was worse than the postoperative best visual acuity(three lines or more) in group 1, 29% in group 2, and 14% in group 3. The causes of worsening in vision were optic or macular atrophy. CONCLUSIONS: Vitrectomy for complications of proliferative diabetic retinopathy is valuable in improving the patient's visual acuity.

Adult↗

PubMed2001

[Tissue platinum distribution and the effect following intra-arterial injection of cisplatin to metastatic liver cancer--a case report].

A 63-year-old male with advanced esophageal cancer was admitted to our hospital. He received neoadjuvant chemotherapy with intravenous cisplatin and fluorouracil (5-FU), and underwent resection of the esophagus and placement of a gastric tube. Two months later, multiple metastases appeared in the right lobe of the liver. Intermittent arterial infusion chemotherapy with cisplatin and 5-FU were performed. To selectively infuse the drugs into the right hepatic artery, the left hepatic artery was embolized. Treatment had a marked effect in the right lobe, but new lesions were subsequently discovered in the left lobe. The patient died of pleuritis 27 days after the end of cisplatin infusion and 12 months after surgery. In total, 465 mg of cisplatin and 20 mg of nedaplatin were administered. At autopsy, tissue samples were collected to measure the platinum concentration. The result showed the highest value to be in the right lobe, 4.8 times as high as that in the left lobe. It is suggested that the concentration of platinum in tissue is correlated with the anticancer effect of cisplatin to the tissue, despite of the traditional view that the tissue concentration and the effect are not related.

Antineoplastic Agents↗

PubMed2001

Beneficial effect of balloon-induced pulsatility on brain oxygenation in hypothermic cardiopulmonary bypass.

BACKGROUND: Sufficient O2 delivery to meet the demand is an important factor for protecting the brain during cardiopulmonary bypass (CPB). This study was designed to investigate the influences of temperature, pulsatility of blood flow (intra-aortic balloon pump-induced) and flow rate during CPB on the cerebral oxygenation. METHODS: Patients were divided into five groups. Normothermia (36 degrees C): pulsatile (n=8, 2.5 L/min/m2), nonpulsatile (n=12, 2.5 L), and nonpulsatile perfusion (n=12, 2.8 L); hypothermia (30 degrees C): pulsatile (n=9, 2.5 L) and nonpulsatile perfusion (n=11, 2.5 L). The oxygen saturation (SjVO2), lactate and CPK-BB levels in the jugular venous blood were measured. RESULTS: In all of the normothermic groups, the SjVO2 value decreased during the CPB (p<0.1-0.01). No remarkable change was observed in the hypothermic groups, with the exception during the rewarming period in the nonpulsatile group. A higher SjVO2 and a lower frequency of SjVO2 values <50% were observed in the hypothermic pulsatile group, as compared with those in the normothermic groups (p<0.05). The levels of CPK-BB were nearly the same, however the levels of lactate were higher in the normothermic pulsatile and nonpulsatile (2.5 L) groups (p<0.05). CONCLUSIONS: We concluded that the hypothermic CPB was advantageous over normothermic CPB in regard to the SjVO2 levels and lactate production. The beneficial effect of intra-aortic balloon pump assist was only obtained in the hypothermic CPB.

Aged↗

PubMed2001

New genome type of adenovirus serotype 19 causing nosocomial infections of epidemic keratoconjunctivitis in Japan.

Twelve strains of adenovirus serotype 19, isolated from cases of epidemic keratoconjunctivitis in Japan in 1992, 1993, 1997, and 1998, were analyzed by DNA restriction analysis, using restriction endonucleases BamHI, BglI, BglII, EcoRI, HindIII, KpnI, PstI, SacI, SalI, SmaI, and XhoI. Among these 11 restriction endonucleases, EcoRI, PstI, SacI, and SmaI were discriminative enzymes, showing restriction patterns different from those reported previously for the prototype and the variant 19a. This new genome type was isolated in 1997 and 1998, when an increase of epidemic keratoconjunctivitis cases caused by adenovirus serotype 19 was observed for both sporadic and nosocomial infections. Strains from 1992 and 1993 showed restriction patterns similar to those of the worldwide reported variant 19a for all enzymes used. The changes detected in strains from 1997 and 1998 could be the reason for the recent epidemic.

Adenovirus Infections, Human↗

PubMed2001

Heparin and heparan sulfate inhibit extracellular signal-regulated kinase activation and myocardial cell hypertrophy induced by endothelin-1.

Heparan sulfate (HS) is one of the components of extracellular matrix and a potent anti-growth factor in various cells. Heparin has a similar structure to HS and is demonstrated to inhibit myocardial cell hypertrophy. We examined the intracellular signal mechanisms linking to the inhibitory effects of heparin and HS on endothelin-1 (ET-1)-induced hypertrophy in cultured rat neonatal myocardial cells (MCs). Heparin inhibited ET-1-induced c-fos mRNA expression. Heparin and HS inhibited ET-1-induced activation of c-fos promoter/enhancer in MCs. Although heparin and HS inhibited ET-1-induced activation of the wild-type c-fos serum response element (SRE), the activation of a mutated c-fos SRE that contains an intact binding site for the serum response factor (SRF) but lacks the ternary complex factor (TCF) binding site, was not inhibited. In addition, heparin and HS inhibited the activation of TPA response element (TRE). However, heparin did not inhibit the activation of cyclic AMP response element (CRE). Furthermore, heparin and HS inhibited ET-1-induced activation of extracellular signal-regulated kinase (ERK) and phosphorylation of Elk-1, which is one of the TCFs. These results indicate that heparin and HS inhibited ET-1-induced ERK activation, resulting in suppression of Elk-1 phosphorylation, and lead to inhibition of c-fos gene expression through SRF-independent manner. Moreover, heparin and HS inhibited ET-1-induced [3H] leucine incorporation. These results suggest that heparin and HS inhibit ET-1 induced myocardial cell hypertrophy through the inhibition of gene expression and protein synthesis.

Amino Acids↗

PubMed2000

JNK activation is associated with intracellular beta-amyloid accumulation.

c-Jun has been implicated in the pathogenesis of Alzheimer's disease (AD), but the upstream cascade leading to c-Jun activation in AD is not known. Activation of c-Jun N-terminal kinase (JNK) is obviously a candidate for the upstream event. We tested this possibility focusing on PS1-linked AD. First, we observed that JNK is actually activated in cerebral neurons of PS1-linked AD patients, using immunohistochemistry and Western blot analyses with anti-activated JNK antibodies. We analyzed the relationship between beta-amyloid (beta A) and JNK activation by using aged transgenic mice overexpressing mutant (M146L) PS1 and human AD brains. The mice showed no neuronal loss but a very few diffuse beta A deposits, corresponding to the early stage of PS1-linked AD brain. Some neurons were reactive for anti-beta A antibodies in the cerebral cortex. Interestingly, JNK activation was observed in neurons showing intracellular beta A immunoreactivity in transgenic mice. Association between intracellular beta A and JNK activation was confirmed in cortical neurons of sporadic and PS1-linked AD patients. Furthermore, introduction of beta A peptides into the primary culture cortical neurons induced JNK activation and cell death. Collectively, these results suggested that intracellular beta A accumulation might trigger JNK activation leading to neuronal death.

Alzheimer Disease↗

PubMed2000

Transmembrane phosphoprotein Cbp positively regulates the activity of the carboxyl-terminal Src kinase, Csk.

Csk (carboxyl-terminal Src kinase) is a cytoplasmic tyrosine kinase that phosphorylates a critical tyrosine residue in each of the Src family kinases (SFKs) to inhibit their activities. Recently, we identified a transmembrane protein, Cbp (Csk-binding protein), that, when phosphorylated, can recruit Csk to the membrane where the SFKs are located. The Cbp-mediated relocation of Csk to the membrane may play a role in turning off the signaling events initiated by SFKs. To further characterize the Csk-Cbp interaction, we have generated a reconstituted system using soluble, highly purified proteins. Csk and phosphorylated Cbp were co-purified as a large protein complex consisting of at least four Csk.Cbp units. The addition of the phosphorylated, but not nonphosphorylated, Cbp to an in vitro assay stimulated Csk activity toward Src. Csk was also activated by a phosphopeptide containing the tyrosine in Cbp that binds to Csk (Tyr-314). Kinetic analysis revealed that Cbp or the phosphopeptide induced up to a 6-fold reduction in the K(m) for Src, indicating that the Csk.Cbp complex has a greater affinity for Src than free Csk. These findings suggest that Cbp is involved in the regulation of SFKs not only by relocating Csk to the membrane but also by directly activating Csk.

Animals↗

PubMed2000

Vitrectomy for the Treatment of Expulsive Hemorrhage.

Purpose: An evaluation of surgical outcome of vitrectomy in the treatment of expulsive hemorrhage associated with intraocular surgery.Methods: We reviewed 12 eyes from 12 patients with expulsive hemorrhage, occurring after or during cataract extraction (4 eyes), phacoemulsification (2 eyes), glaucoma filtering surgery (4 eyes), or vitrectomy (2 eyes). Mean follow-up period was 21 months.Results: The retina was reattached in 6 eyes (50%) after the initial surgery and ultimately in 9 eyes (75%). Three eyes, which failed to achieve retinal reattachment, resulted in phthisis bulbi. Final visual acuity was 0.1 or better in 4 eyes and 0.01 to 0.09 in 4 eyes. The incidence of expulsive hemorrhage was 0% for cataract surgery, 0.57% for trabeculectomy, and 0.09% for vitrectomy at Toho University Sakura Hospital.Conclusion: In the treatment of expulsive hemorrhage, vitrectomy is an effective surgical procedure to improve the visual function.

Journal Article↗

PubMed2000

Alexia caused by a fusiform or posterior inferior temporal lesion.

We evaluated the alexia and agraphia of three patients with different lesions using Japanese kanji (morphograms) and kana (phonograms) and made a lesion-to-symptom analysis. Patient 1 (pure alexia for both kanji and kana and minor agraphia for kanji after a fusiform lesion) made more paragraphic errors for kanji, whereas patient 2 (alexia with agraphia for kanji after a posterior inferior temporal lesion) showed severe reading and writing disturbances and more agraphic errors for kanji. Brodmann Area 37 was affected in both patients, but in patient 2 the lesion was located lateral to that in patient 1. Patient 3 showed agraphia without alexia after restricted lesion to the angular gyrus. We believe that pure alexia (patient 1) results from a disconnection between the medial fusiform gyrus and posterior inferior temporal area (the lateral fusiform and inferior temporal gyri), whereas alexia with agraphia for kanji (patient 2), corresponding to lexical agraphia in Western countries, results from damage to the posterior inferior temporal area, in which whole-word images of words are thought to be stored. Furthermore, restricted lesion in the angular gyrus (patient 3) does not produce alexia; the alexic symptom of "angular" alexia with agraphia may be the result of damage to the adjacent lateral occipital gyri.

Aged↗

PubMed2000

Secretion, gamma-carboxylation, and endoplasmic reticulum-associated degradation of chimeras with mutually exchanged Gla domain between human protein C and prothrombin.

Warfarin, an antagonist of vitamin K, causes diminution of vitamin K-dependent coagulation factors in the circulation. Although all vitamin K-dependent factors have Gla domains, the warfarin-induced decrease in their plasma concentration differs among factors. In warfarin-treated HepG2 cells, we found modest and severe intracellular degradation of prothrombin and protein C, respectively. To investigate the structural features of these proteins that contribute to their warfarin sensitivity, chimeric prothrombin containing the prepropeptide and Gla domain of protein C was expressed in baby hamster kidney (BHK) cells. This chimera showed similar secretion kinetics and warfarin sensitivity to those of wild-type prothrombin, demonstrating that the Gla domain cannot solely explain the warfarin sensitivity of protein C. In contrast, two chimeric protein Cs containing either the Gla domain alone or the prepropeptide and Gla domain of prothrombin showed impaired secretion. Even though gamma-carboxylation proceeded normally, both chimeras were degraded intracellularly by the proteasome. From these results, we conclude that not only the folding of the Gla domain, but the entire structure and conformation of protein C and prothrombin, contribute to their quality control and susceptibility to warfarin-induced ER (endoplasmic reticulum)-associated degradation.

Adenosine Triphosphatases↗

PubMed2000

High resolution transmission electron microscopy observation of thermally fluctuating phasons in decagonal Al-Cu-Co

In situ high-temperature, high resolution transmission electron microscopy (HRTEM) was performed on an Al-Cu-Co decagonal quasicrystal, to investigate thermal fluctuation of phasons. A tiling pattern constructed from the HRTEM image was analyzed in the framework of the strip-projection method. Transitions between two local tile arrangements were observed at high temperature for the first time, and were shown to correspond to a thermal phason fluctuation.

Journal Article↗

PubMed2000

Protective effect of microglial conditioning medium on neuronal damage induced by glutamate.

To examine the effect of microglial conditioning medium (MCM) on damaged neurons, cultured neurons exposed to glutamate were incubated with MCM. More neurons survived in these groups, particularly in the case of glutamate stimulation of microglia. Therefore cultured neurons exposed to glutamate were incubated with MCM at predetermined intervals after glutamate stimulation. Neuronal cultures using MCM at 1, 2 and 6 h after glutamate stimulation had more surviving cells than those using unstimulated MCM. Neuronal cultures using MCM at 12 and 24 h had as much surviving cells as those using unstimulated MCM. These results indicate that the neuroprotective effect of microglia appears only in the early phase after treatment of glutamate and disappears in the late phase.

Animals↗

PubMed2000

PQBP-1/Npw38, a nuclear protein binding to the polyglutamine tract, interacts with U5-15kD/dim1p via the carboxyl-terminal domain.

PQBP-1 was identified as a binding protein to the polyglutamine tract present in various transcription-related factors and causative genes for neurodegenerative disorders. This novel gene contains at least two functional domains, WW domain and carboxyl-terminal domain (CTD), strictly conserved beyond species. Although human PQBP-1 additionally contains the polar amino acid-rich domain by which it binds to the polyglutamine tract, genuine physiological function(s) have not been clarified. In this study, we showed that U5-15kD, human homologue of fission yeast dim1p, is a partner molecule of PQBP-1 binding to CTD. This finding suggests physiological functions of PQBP-1 in splicing, cell cycle, and ubiquitination, through which we can speculate the pathological roles of PQBP-1 in triplet repeat diseases.

Amino Acid Sequence↗

PubMed2000

Decreased UV sensitivity, mismatch repair activity and abnormal cell cycle checkpoints in skin cancer cell lines derived from UVB-irradiated XPA-deficient mice.

Xeroderma pigmentosum group A gene (XPA)-deficient mice are defective in nucleotide excision repair (NER) and are therefore highly sensitive to ultraviolet (UV)-induced skin carcinogenesis. We established cell lines from skin cancers of UVB-irradiated XPA-deficient mice to investigate the phenotypic changes occurring during skin carcinogenesis. As anticipated, the skin cancer cell lines were devoid of NER activity but were less sensitive to killing by UV-irradiation than the XPA(-/-) fibroblast cell line. The lines were also more resistant to 6-thioguanine (6-TG) than XPA(-/-) and XPA(+/+) fibroblasts, which was suggestive of a mismatch repair (MMR) defect. Indeed, in vitro mismatch binding and MMR activity were impaired in several of these cell lines. Moreover, these cell lines displayed cell cycle checkpoint derangements following UV-irradiation and 6-TG exposure. The above findings suggest that MMR downregulation may help cells escape killing by UVB, as was seen previously for methylating agents and cisplatin, and thus that MMR deficient clones are selected for during the tumorigenic transformation of XPA(-/-) cells.

Animals↗

PubMed2000

Studies of in vivo mutations in rpsL transgene in UVB-irradiated epidermis of XPA-deficient mice.

We have established xeroderma pigmentosum group A (XPA) gene-knockout mice with nucleotide excision repair (NER) deficiency, which rapidly developed skin tumors when exposed to a low dose of chronic UV like XP-A patients, confirming that the NER process plays an important role in preventing UVB-induced skin cancer. To examine the in vivo mutation in the UVB-irradiated epidermis, we established XPA (-/-), (+/-) and (+/+) mice carrying the Escherichia coli rpsL transgene with which the mutation frequencies and spectra in the UVB-irradiated epidermal tissue can be examined conveniently. The XPA (-/-) mice showed a higher frequency of UVB-induced mutation in the rpsL transgene with a low dose (150 J/m(2)) of UVB-irradiation than the XPA (+/-) and (+/+) mice, while, at a high dose (900 J/m(2)) they showed almost the same frequency of mutation as the XPA (+/-) and (+/+) mice, probably because of cell death in the epidermis of the XPA (-/-) mice. However, CC-->TT tandem transition, a hallmark of UV-induced mutation, was detected at higher frequency in the XPA (-/-) mice than the XPA (+/-) and (+/+) mice at both doses of UVB. This rpsL/XPA mouse system will be useful for further analyzing the role of NER in the mutagenesis and carcinogenesis induced by various carcinogens.

Animals↗

PubMed2000

More than 95% reversal of left-right axis induced by right-sided hypodermic microinjection of activin into Xenopus neurula embryos.

In recent years, genes that show left-right (L-R) asymmetric expression patterns have been identified one after another in vertebrate gastrula-neurula embryos. However, we still have little information about when the irreversible L-R specification is established in vertebrate embryos. In this report, we show that almost 100% of the embryos develop to be L-R-inverted larvae after microinjection of activin molecules into the right lateral hypodermic space of Xenopus neurula embryos. After right-side injection of 10-250 pg activin protein, both early neurulae just after gastrulation movement (stage 13-14) and late neurulae just before neural tube closure (stage 17-18) showed almost 100% reversal of the heart and gut L-R axes. At higher doses of activin, more than 90% of the L-R-inverted embryos showed L-R reversal of both heart and gut. The survival ratio of the right-injected 4-day embryos was 90% on average. In the left-injected embryos, the occurrence of L-R inversion was less than 2% as observed in normal untreated siblings (1.7%). When the same amount of activin (1-50 pg) was microinjected into both sides of neurula embryos, the incidence of L-R inversion was reduced to 58%. The injection of activin along the dorsal midline in the trunk region also randomized the visceral L-R axis. Injection of activin into the right side changed normal left-handed expression of Xnr-1 to right-handed or bilateral expression. In contrast, left-handed expression of Pitx2 was switched to the right side by right activin injection. This is the first report of a method that achieves complete inversion of the visceral L-R axis by treatment of embryos at the neurula stage. Activin not only acts on the neurulae to cancel the original L-R specification up to the late neurula stage, but also rebuilds a new L-R axis whose left side coincides with the injection side. It is suggested that the left and right halves of neurulae have equal potential for L-R differentiation.

Activins↗

PubMed2000

mRNA encoding 'ClC-K1, a kidney Cl(-)- channel' is expressed in marginal cells of the stria vascularis of rat cochlea: its possible contribution to Cl(-) currents.

The cochlear stria vascularis is essential for the normal function of hair cells. mRNA encoding the ClC-K1 Cl(-) channel, previously thought to be found only in the kidney, was detected in epithelial marginal cells of the rat stria vascularis by single cell RT-PCR. When Cl(-) currents were recorded from rat marginal cells by the whole-cell patch clamp method, the steady-state currents showed weak outward rectification and an ion selectivity sequence of SCN(-)Br(-)=Cl(-)F(-)NO(3)(-)I(-)gluconate(-). The Cl(-) currents were regulated by extracellular Ca(2+) and pH. These characteristics resemble those reported for the currents recorded from Xenopus oocytes expressing ClC-K1 Cl(-) channels. These data together suggest that ClC-K1 Cl(-) channels may contribute to the whole-cell currents of marginal cells.

Animals↗