[GAT (galactosyltransferase associated with tumor)].
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Biomarkers, Tumor↗
Biomedical subjects
T Fukuchi
Publications and source records attributed to T Fukuchi.
[Studies on brain pyruvate dehydrogenase (PDH) activity and energy metabolites during ischemia and reperfusion].
Pyruvate dehydrogenase is one of the mitochondrial enzymes considered important in the regulation of oxidative metabolism. To further understand the relationship between its activity and ischemic brain damage we conducted three experiments. We studied the effects of (1) duration of cerebral ischemia, (2) the Ca2+ channel blocker, nicardipine, and (3) the immunosuppressant, FK506, on PDH activity and energy metabolites during ischemia and reperfusion. In the first study we also measured regional cerebral blood flow (rCBF). (1) Increasing the duration of the ischemic insult delayed the deactivation of PDH, slowed the resynthesis of high energy phosphates and the clearance of lactate, and impaired recovery of rCBF. Additionally, (2) nicardipine normalized PDH activities and improved the impaired metabolism after reperfusion, and (3) FK506 did not effect PDH activity, but significantly improved the impaired metabolism during the early phase of reperfusion. From these studies we conclude that PDH plays a role in the recovery of metabolism during reperfusion, and both nicardipine and FK506 improve metabolism during the early phase of reperfusion.
Animals↗
Beta-catenin mutation in carcinoma of the uterine endometrium.
Beta-catenin forms complexes with Tcf and Lef-1 and functions as a transcriptional activator downstream of the Wnt signaling pathway. Activation of the pathway by stabilization of beta-catenin has been shown to be important in the development of colorectal carcinoma, which is mainly caused by inactivating mutations of the adenomatous polyposis coli tumor suppressor gene or by activating mutations in exon 3 of the beta-catenin gene. Here, we analyzed mutations in exon 3 of the beta-catenin gene in endometrial carcinoma cases in which loss of heterozygosity at the adenomatous polyposis coli tumor suppressor gene locus has been rarely reported. We found that 10 of 76 cases had beta-catenin gene mutations. All mutations identified were single-base missense mutations on serine/threonine residues (codons 33, 37, 41, and 45), altering the glycogen synthase kinase-3beta phosphorylation consensus motif, which participates in the degradation of beta-catenin. To determine whether these beta-catenin mutations actually led to stabilization of this protein, expression of beta-catenin was analyzed immunohistochemically, and 9 of 10 cases with the beta-catenin mutation and 20 of 66 cases without it showed accumulation of beta-catenin in the cytoplasm and/or nucleus. In total, 38% of cases showed accumulation of beta-catenin. These data indicate that stabilization of beta-catenin due to mutations in exon 3 of the beta-catenin gene and other mechanisms may have an important role in development of endometrial carcinomas.
Adult↗
The effect of duration of cerebral ischemia on brain pyruvate dehydrogenase activity, energy metabolites, and blood flow during reperfusion in gerbil brain.
The objective of this study was to determine whether the duration of an ischemic insult effects the activity of the mitochondrial enzyme pyruvate dehydrogenase (PDH) in relation to the recovery of metabolites and regional cerebral blood flow (rCBF) immediately after ischemia and during reperfusion in gerbil cortex. Cerebral ischemia was induced, using the bilateral carotid artery occlusion method, for 20 or 60 min, followed by reperfusion up to 120 min. Immediately after ischemia PDH activity increased threefold regardless of ischemic duration. In the 60-min ischemic group, PDH remained activated, the recovery of high energy phosphates and the clearance of lactate were poor, and the rCBF was 48% of controls after 20-min reperfusion, decreasing gradually to 26% at 120-min reperfusion. In the 20-min ischemic group, PDH activity normalized quickly, the restoration of energy phosphates was good, there was a quick reduction in lactate within the first 60 min of reperfusion, and the rCBF was 65% of control at 20-min reperfusion, and remained over 48% of control throughout reperfusion. Recovery of metabolism after reperfusion did not parallel the changes in rCBF in either group, most noticeably in the 60-min ischemic group. The slow normalization of PDH activity reflected the poor recovery of metabolites in the 60-min ischemic group, indicating that PDH activity is important in the resynthesis of energy metabolites during reperfusion. In conclusion, prolonging the ischemic insult effected PDH activity during reperfusion, impaired recovery of energy metabolites, and worsened the recovery of rCBF.
Adenosine Triphosphate↗
Effect of hyperglycemia on pyruvate dehydrogenase activity and energy metabolites during ischemia and reperfusion in gerbil brain.
The effects of hyperglycemia on brain pyruvate dehydrogenase (PDH) and metabolites (ATP, PCr, and lactate) were investigated at 20 min ischemia, 0, 20, and 60 min, and 4 h reperfusion. During reperfusion, PDH activities were suppressed corresponding to the poor recovery of ATP and PCr concentrations and the increase in lactate concentration in the hyperglycemic group, suggesting that preischemic hyperglycemia may impair metabolism by suppressing PDH activity.
Adenosine Triphosphate↗
Effect of nicardipine, a Ca2+ channel blocker, on pyruvate dehydrogenase activity and energy metabolites during cerebral ischemia and reperfusion in gerbil brain.
The purpose of this study was to determine if nicardipine, a calcium ion channel blocker, affects pyruvate dehydrogenase (PDH) activity and improves energy metabolism during cerebral ischemia and reperfusion. Cerebral ischemia was induced, using the bilateral carotid artery occlusion method, for 60 min followed by reperfusion up to 120 min in gerbils. Nicardipine (1 mg/kg) or saline (vehicle-treated) was given to gerbils 30 min prior to the occlusion of the common carotid arteries. PDH activity and metabolites (ATP, PCr, and lactate) were measured in cortex prior to ischemia, immediately following ischemia, and after each reperfusion period. After 60 min ischemia, PDH activity increased in both groups, and was significantly higher in the nicardipine-treated group. After 20 min reperfusion, PDH activity in the nicardipine-treated group recovered to control levels, whereas, the PDH activity in the vehicle-treated group remained elevated, and was higher than the nicardipine-treated animals. At 60 and 120 min reperfusion, the activities in the vehicle-treated group were significantly below control levels, there were no differences, however, between the two groups. ATP and PCr concentrations were markedly depleted immediately after ischemia in both groups. ATP levels at 20 min reperfusion and PCr levels at 60 min reperfusion were significantly higher in the nicardipine-treated group. Lactate concentrations in both groups increased 7-8 fold, similarly, immediately after ischemia. During reperfusion, the lactate remained elevated in both groups, though the levels in the nicardipine-treated group were lower than those in the vehicle-treated group, but not significantly. Nicardipine treatment normalized PDH activity quickly and improved energy metabolism after reperfusion.
Animals↗
Three-dimensional scanning electron microscopic study of keratoconus corneas.
OBJECTIVE: To examine the 3-dimensional collagen fibril organization in the Bowman layer of keratoconus corneas. METHODS: Eight keratoconus corneas, 8 corneas with other diseases, and 5 normal human corneas were studied. A cell maceration method in combination with scanning electron microscopy was used to examine the collagen network in the Bowman layer. RESULTS: In normal corneas, the surface of the Bowman layer was smooth and collagen fibrils were regularly arranged. By contrast, sharply edged defects in the Bowman layer were found in keratoconus corneas. Lattice-like configurations of the ruptured Bowman layer and collagenous scar tissue were observed, to varying degrees, in all keratoconus corneas examined. None of the other diseased corneas exhibited the ruptures. CONCLUSIONS: Scanning electron microscopy demonstrated alterations in the Bowman layer specific to keratoconus. Fragmentation of the Bowman layer may be an early change leading to keratoconus conditions.
Adolescent↗
Influence of intermittent ischemia on thioacetamide-induced rat liver cirrhosis.
We studied the influence of intermittent ischemic injury on thioacetamide-induced liver cirrhosis in rats. Wistar rats were divided into group A, intermittent ischemic injury to liver cirrhosis, and group B, continuous ischemic injury to liver cirrhosis. Total ischemic time was 60 min in both groups. In group A, ischemic injury consisted of a repetition 4 times of 15 min ischemia and 5 min reperfusion. The ATP level of the liver was measured before ischemia, before reperfusion, and 60 min after reperfusion. Bile was collected to determine bile flow rate. The ATP level in the liver tissue 60 min after reperfusion was significantly (p < 0.05) higher in group A than in group B. The ATP level immediately before reperfusion was also significantly (p < 0.05) higher in group A than in group B. The survival rate 1 week after ischemic injury and bile flow rate 60 min after reperfusion were significantly (p < 0.01) higher in group A compared with those in group B. The energy level was much higher in intermittent ischemic injury than in continuous ischemic injury immediately before reperfusion and after reperfusion. Survival rate and bile flow rate were higher in intermittent ischemic injury than in continuous ischemic injury. Therefore it suggests that the viability of the liver was maintained better in intermittent ischemic injury than in continuous ischemic injury.
Adenosine Triphosphate↗
[Experimental glaucoma model in the rat with laser trabecular photocoagulation after intracameral injection of India ink].
We tried to create an experimental glaucoma which is simple and highly reproducible in rodents. India ink was injected into the anterior chamber with a 30-gauge needle. The carbon particles were trapped in the chamber angle and formed a black band along the corneal limbus one week later. This area was then photocoagulated anteroposteriorly with an argon laser. Photocoagulation was repeated until the intraocular pressure was elevated to 25 mmHg or more by pneumotonometry performed at a one-week interval. The above procedure was applied to one eye of 7 rats with the fellow eye serving as control. Chronic elevation of intraocular pressure was obtained in all the 7 treated eyes. The eyes were then enucleated and examined by light microscopy. Carbon particles were phagocytosed by macrophages in the intertrabecular spaces. Peripheral anterior synechias were also present. The optic nerve-head showed remarkable decrease in nerve fibers and cavernous degeneration suggestive of glaucomatous optic nerve damage. This experimental model promises to be of value in further studies of glaucomatous optic nerve damage.
Animals↗
[Influences of trabeculectomy combined with the use of mitomycin C on corneal endothelial cells].
We used a specular microscope to evaluate the corneal endothelial cells in 119 eyes before and 2 to 3 weeks after trabeculectomy with topical mitomycin C. The endothelial cell density per square millimeter averaged 2,569 +/- 487 (mean +/- standard deviation) before surgery and 2,444 +/- 536 after surgery, showing a decrease of 4.98%. The hexagonality decreased by 1.7%, the coefficient of variation increased by 1.9, and the average cell area increased by 6.82%. There were no statistical differences as a whole in these values. Decrease in hexagonality was more frequent in eyes with prior intraocular or glaucoma surgery. Eyes treated by laser trabeculoplasty showed a decrease in endothelial cell density, an increase in coefficient of variation and an increase in hexagonality. Eyes with postoperative flat anterior chamber showed significant changes in each parameter. The findings show that trabeculectomy with topical mitomycin C does not significantly affect the corneal endothelial cells at 2 to 3 weeks after surgery.
Administration, Topical↗
[Glaucoma with microcornea; morphometry and differential diagnosis].
To evaluate the characteristics of 10 glaucomatous cases with microcornea, we measured corneal diameter, curvature, axial length, and depth of anterior chamber, and examined the eyes with a specular microscope and an ultrasound biomicroscope. The ten cases examined in this study included 1 case of cornea plana, 2 cases of sclerocornea, 2 cases of nanophthalmos, and 5 cases of anterior microphthalmos. Three of the 10 cases were combined with open angle glaucoma, and the others with closed angle glaucoma. Open-angle glaucoma seemed like developmental glaucoma with angle maldevelopment. The closed angle type may appear at a younger age than in patients who have simple pupilary block. There are probably complex mechanisms related with closed angle glaucoma with microcornea. While differential diagnosis among these cases is relatively easy, we should evaluate how or why the intraocular pressure rises as far as possible before forming a treatment plan for each patient.
Adolescent↗
Effects of mitomycin C on the expression of proliferating cell nuclear antigen after filtering surgery in rabbits.
BACKGROUND: The aim of the study was to evaluate the effects of mitomycin C on the cell replication activity in wound healing following experimental filtration surgery. METHODS: Trabeculectomy with or without application of mitomycin C was performed on albino rabbit eyes. At 1, 4, 7, 14, and 28 days after surgery, the expression of proliferating cell nuclear antigen, a marker of cell proliferation, in the filtering site was examined immunohistochemically using a streptavidin-biotin complex method. RESULTS: In control eyes that underwent trabeculectomy but did not receive mitomycin C, the number of immunoreactive cells increased 4-7 days after operation and decreased markedly at around 14 days. The filtering site was obstructed histologically at 4-7 days after operation. In the mitomycin C-treated eyes, immunoreactive cells appeared 4 days after surgery but disappeared by 7 days at the surgical site. The number of immunoreactive cells in the treated eyes was much lower than that in control eyes. CONCLUSION: The cell replication activity was markedly inhibited by administration of mitomycin C. The filtering site remained open for 28 days after surgery, whereas it was completely obstructed within 7 days in control eyes. Immunocytochemistry for proliferating cell nuclear antigen, as used in this study, is a simple and reliable method for detection of cell replication activity.
Animals↗
[Distribution of cell adhesion glycoproteins in the human retrobulbar optic nerve].
We examined the immunohistochemical distribution of six types of cell adhesion glycoproteins in the human retrobulbar optic nerve. The pial septa had laminin and entactin on the surface at the border with the optic nerve fibers, and fibronectin and vitronectin were distributed in the stroma of the septa. Some tenastin was also detectable both on the surface and in the stroma of the septa. Thrombospondin was associated with capillaries within the stroma. The surface of the arachnoid membrane, the pia mater, and the dura mater was covered by laminin and entactin. Diffuse staining with antifibronectin antibody was seen in all these meningeal tissues, but vitronectin showed a fine fibrillar appearance in these tissues. No significant staining could be found for tenastin. Thrombospondin showed only faint staining on the capillaries of the pia mater and the dura mater. These findings can provide clues for the discussion of how the extracellular matrix works and what roles it plays in disorders involving the retrobulbar optic nerve, such as optic neuritis and glaucoma.
Cell Adhesion↗
Cathepsin G, acid phosphatase, and alpha 1-proteinase inhibitor messenger RNA levels in keratoconus corneas.
PURPOSE: Keratoconus is characterized by thinning and scarring of the central region of the cornea. The authors have shown, in corneas obtained from patients with keratoconus, that lysosomal enzyme activities are elevated, whereas levels of protease inhibitors such as alpha 1-proteinase inhibitor (alpha 1-PI) are reduced. This study was undertaken to examine further the gene expression of cathepsin G, acid phosphatase, and alpha 1-PI in keratoconus corneas. METHODS: Corneal buttons were collected from patients with keratoconus, normal subjects, and patients with other corneal diseases. In situ hybridization was performed on paraffin sections using a tritium-labeled probe for cathepsin G or alpha 1-PI. Competitive polymerase chain reaction (PCR) was used to determine the messenger RNA (mRNA) levels for lysosomal acid phosphatase and alpha 1-PI in epithelial and stromal cells of keratoconus corneas. RESULTS: Silver grains, indicative of positive in situ hybridization products, were observed in all three cell types of normal corneas for both DNA probes. Compared with normal and other diseased controls, the labeling was enhanced for cathepsin G but was diminished for alpha 1-PI in the epithelium of keratoconus corneas. Competitive PCR showed that the mRNA level for acid phosphatase was higher and that the mRNA level for alpha 1-PI was lower in keratoconus corneas. CONCLUSIONS: These results indicate that the mRNA level for degradative enzymes in increased and that for alpha 1-PI it is reduced in keratoconus corneas. This study provides the first evidence that the altered expression of multiple enzymes and inhibitors in keratoconus occurs at the gene level. Furthermore, it implicates a possible role of coordinated transcriptional regulation of gene expressions in keratoconus.
Acid Phosphatase↗
[Expression of proteinase inhibitors in the human trabecular meshwork].
We examined the distribution and expression of three proteinase inhibitors, alpha 1-proteinase inhibitor (alpha 1-PI), alpha 1-antichymotrypsin (alpha 1-ACT), and alpha 2-macroglobulin (alpha 2-M) in the human trabecular meshwork. Immunohistochemistry, in situ hybridization, and reverse transcription-polymerase chain reaction (RT-PCR) were used. By immunostaining, all three inhibitors were identified in the human trabecular meshwork with enhanced staining in the uveal meshwork. In situ hybridization showed mild but positive accumulation of the silver grains on the trabecular meshwork cells, which indicates mRNA expression. Specific distribution or cell selectivity were not detectable probably due to weak expression of these inhibitors in this tissue. Instead mRNAs for alpha 1-PI, alpha 1-ACT, and alpha 2-M as well as antithrombin III, plasminogen activator inhibitor-1 could be identified by RT-PCR using trabecular meshwork culture cells. In this study, we concluded that some proteinase inhibitors were distributed in the human trabecular meshwork as well as in the cornea and the ciliary body. At least part of these were probably produced by the trabecular meshwork cells. The balance between proteinases and proteinase inhibitors might play an important role even in the human trabecular meshwork to maintain the outflow route. The alterations in the primary or secondary glaucomatous eyes are curious.
Adolescent↗
[Plateau iris configuration as a risk factor for malignant glaucoma].
To provide evidence for diagnosing malignant glaucoma, as well as to elucidate the pathogenetic mechanism of the disease, ultrasound biomicroscopy (UBM) is a useful tool. We examined the anterior segments of three patients with post-operative malignant glaucoma with UBM regarding the state before operation, the state of the opposite eye, and the state after the release of the cilio-lenticular block. Case 1 was a 76-year-old female who was diagnosed as having chronic angle-closure glaucoma (CACG) and was treated by trabeculectomy, phacoemulsification, aspiration (PEA), and simultaneous intraocular lens (IOL) implantation. Case 2 was a 22-year-old male diagnosed as having CACG secondary to plateau iris syndrome and was treated by trabeculectomy. Case 3 was a 73-year-old female diagnosed as having normal-tension glaucoma with narrow angle and was treated by PEA and IOL implantation. Slit-like anterior chamber angle and anteriorly positioned ciliary body were observed in all 3 cases, which were identical to those Pavlin reported in 8 cases with plateau iris syndrome. UBM seems to be an important pre-operative examination to evaluate the risk of malignant glaucoma and to consider which surgical procedure and post-operative management is proper. The pre-operative configuration of the ciliary body may be associated with the onset of malignant glaucoma in some patients with CACG or narrow angle.
Adult↗
The Saccharomyces cerevisiae SSD1 gene is involved in the tolerance to high concentration of Ca2+ with the participation of HST1/NRC1/BFR1.
The SSD1 gene of Saccharomyces (S.) cerevisiae is a polymorphic gene involved in many aspects of the yeast cell growth (Sutton et al., 1991). We found that ssd1 null mutant shows increased sensitivities of growth to trifluoperazine (TFP) and high concentration of Ca2+. A high-copy suppressor gene, HST1, for the TFP and Ca2+ sensitivities of ssd1 null mutant was cloned and sequenced. The HST1 gene encodes a polypeptide of 915 amino acids, and is identical to the NRC1/BRF1 gene in databases. The HST1 disrupted cells were viable, but they grew slowly in the presence of high levels of Ca2+, with notable morphological change. In addition, disruption of the gene in a ssd1 null mutant further increased the sensitivities of the cells to TFP and Ca2+. The results indicated the possibility that the SSD1 gene is involved in the tolerance mechanism to high concentration of Ca2+, and the HST1 gene participates with SSD1 by its functional redundancy in Ca2+ tolerance.
Alleles↗
Interictal cerebral and cerebellar blood flow in temporal lobe epilepsy as measured by a noninvasive technique using Tc-99m HMPAO.
The usefulness of noninvasive regional cerebral blood flow measurements using Tc-99m hexamethylpropylene amine oxime (HMPAO) was evaluated in 45 patients with interictal temporal lobe epilepsy. Seizure frequency did not show any influence on flow values or side-to-side asymmetry. Patients taking phenytoin had a significantly lower mean cerebral blood flow (mean 9.5%) and lower mean cerebellar blood flow (mean 12.9%) than those not taking it. Moreover, phenytoin reduced regional cerebral blood flow in the temporal regions more prominently on the contralateral side of the epileptic focus than on the ipsilateral side. Positive MRI findings of hippocampal sclerosis along with visually detected temporal hypoperfusion on SPECT showed a lower regional cerebral blood flow and greater flow asymmetry than other imaging findings in the temporal region. Results suggest that noninvasive cerebral blood flow measurements using Tc-99m HMPAO may give useful information about interictal cerebral blood flow around an epileptic focus and about the effects of antiepileptic drugs on brain function in temporal lobe epilepsy.
Adolescent↗