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Akira Kobayashi

Publications and source records attributed to Akira Kobayashi.

At least 19 recordsLinked to original sources
PubMed2003

Photoreceptor synaptic protein HRG4 (UNC119) interacts with ARL2 via a putative conserved domain.

Human retinal gene 4 (HRG4) (UNC119) is a photoreceptor synaptic protein of unknown function, shown when mutated to cause retinal degeneration in a patient and in a confirmatory transgenic model. ADP-ribosylation factor-like protein 2 (ARL2) was identified as an interactor of HRG4 by the yeast two-hybrid strategy. The presence of ARL2 in the retina and co-localization with HRG4 was confirmed by Western blot and double immunofluorescence analysis, respectively. The interaction of ARL2 with HRG4 was further confirmed by co-immunoprecipitation and direct binding analysis. Phosphodiesterase delta (PDEdelta) is an ARL2-binding protein homologous to HRG4. Amino acid residues of PDEdelta involved in binding ARL2 and forming a hydrophobic pocket were shown to be highly conserved in HRG4, suggesting similarity in binding mechanism and function.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Accuracy of intraocular pressure by Tono-Pen XL over amniotic membrane patching in rabbits.

PURPOSE: To report an accuracy of intraocular pressure (IOP) by Tono-Pen XL over amniotic membrane patching in rabbits. DESIGN: Experimental study. METHODS: Seven male albino rabbits were used in this study. After general anesthesia, IOP was measured in both eyes using the Tono-Pen without amniotic membrane. A single layer amniotic membrane was then immediately placed over the rabbit eye, and the IOP measurement was repeated. RESULTS: The average IOP without amniotic membrane was 5.8 +/- 0.6 mm Hg (mean +/- SD). The average IOP through amniotic membrane was 6.0 +/- 0.4 mm Hg (mean +/- SD). There was no statistical difference in IOP measured on corneas with or without the amniotic membrane (P =.34). CONCLUSIONS: The accuracy of IOP measurement by Tono-Pen XL over a single layer of amniotic membrane patching was demonstrated using rabbit eyes. Further studies in human eyes may verify our findings in actual clinical settings.

Amnion↗
PubMed2003

Detection of rabbit corneal epithelium over amniotic membrane patch by white-light and laser confocal microscopy.

PURPOSE: To report confocal microscopic observation of rabbit corneal epithelium through amniotic membrane patch (AMP). DESIGN: Experimental study. METHOD: Six rabbit eyes were patched by amniotic membrane. Then, white-light and laser confocal microscopic observation was performed. RESULTS: Images of human amniotic epithelium, amniotic basement membrane, and amniotic stroma were obtained using both devices, followed by detection of rabbit corneal epithelium. CONCLUSION: This study indicates that observation of corneal epithelium through AMP is possible in rabbit eyes using both these methods. This implies that both devices might be used clinically to observe the epithelial healing process under an AMP to better determine when it should be removed.

Amnion↗
PubMed2003

In vivo confocal microscopy in the patients with cornea farinata.

PURPOSE: To report in vivo corneal confocal microscopic findings of patients with cornea farinata. PATIENTS AND METHODS: Two unrelated patients, a 47-year-old man and a 77-year-old woman, with cornea farinata were studied. Examination with a confocal microscope was performed in addition to routine slit-lamp biomicroscopy. RESULTS: In both cases, slit-lamp biomicroscopy showed numerous small, faint opacities in the deep stroma in both eyes. Using confocal microscopy, highly reflective small particles were observed in the cytoplasm of keratocytes in the deep stroma adjacent to the corneal endothelial layer. No abnormalities could be detected in the epithelial layer, in the mid-stromal layer, at the level of Descemet's membrane, and in the endothelial layer. CONCLUSIONS: In vivo corneal confocal microscopy is useful for observing stromal abnormalities in cornea farinata. Further investigation of posterior stromal opacities using confocal microscopy may be useful to understand and differentiate various corneal conditions involving primarily deep stromal layers.

Aged↗
PubMed2003

Results of surgical resection for patients with hilar bile duct cancer: application of extended hepatectomy after biliary drainage and hemihepatic portal vein embolization.

OBJECTIVE: To evaluate the feasibility of an aggressive surgical approach incorporating major hepatic resection after biliary drainage and preoperative portal vein embolization for patients with hilar bile duct cancer. SUMMARY BACKGROUND DATA: Although many surgeons have emphasized the importance of major hepatectomy in terms of curative resection for patients with hilar bile duct cancer, this procedure results in a high incidence of postoperative morbidity and mortality in patients with cholestasis-induced impaired liver function. METHODS: A retrospective cohort study was conducted in 140 patients with hilar bile duct cancer treated from 1990 through 2001. Resectional surgery was performed in 79 patients, 69 of whom underwent major hepatic resection. Thirteen patients underwent concomitant pancreaticoduodenectomy. Preoperative biliary drainage was carried out in all 65 patients who had obstructive jaundice. Portal vein embolization was conducted in 41 of 51 patients undergoing extended right hepatectomy. Short- and long-term outcomes were evaluated. RESULTS: No patient experienced postoperative liver failure (maximum total bilirubin level, 5.4 mg/dL). The in-hospital mortality rate was 1.3% (1 in 79, resulting from cerebral infarction). A histologically negative resection margin was obtained more frequently when the scheduled extended hepatic resection was conducted (75% vs 44%, P = 0.0178). The estimated 5-year survival rate was 40% when histologically negative resection margins were obtained, but only 6% if the margins were positive. Multivariate analysis identified the resection margin and nodal status as independent factors predictive of survival. CONCLUSIONS: Extensive resection, mainly extended right hemihepatectomy, after biliary drainage and preoperative portal vein embolization, when necessary, for patients with hilar bile duct cancer can be performed safely and is more likely to result in histologically negative margins than other resection methods.

Adult↗
PubMed2003

Functional analysis of basic transcription element binding protein by gene targeting technology.

Basic transcription element binding protein (BTEB) is a transcription factor with a characteristic zinc finger motif and is most remarkably enhanced by thyroid hormone T(3) treatment (R. J. Denver et al., J. Biol. Chem. 272:8179-8188, 1997). To investigate the function of BTEB per se and to touch on the effects of T(3) (3,5,3'-triiodothyronine) on mouse development, we generated BTEB-deficient mice by gene knockout technology. Homologous BTEB(-/-) mutant mice were bred according to apparently normal Mendelian genetics, matured normally, and were fertile. Mutant mice could survive for at least 2 years without evident pathological defects. From the expression of lacZ, which was inserted into the reading frame of the BTEB gene, BTEB showed a characteristic tissue-specific expression profile during the developmental process of brain and bone. Dramatically increased expression of BTEB was observed in Purkinje cells of the cerebellum and pyramidal cell layers of the hippocampus at P7 when synapses start to form in the brain. Although general behavioral activities such as locomotion, rearing, and speed of movement were not so much affected in the BTEB(-/-) mutant mice, they showed clearly reduced activity levels in rotorod and contextual fear-conditioning tests; this finding was probably due to defective functions of the cerebellum, hippocampus, and amygdala.

Amygdala↗
PubMed2003

Decrease in vitamin D receptor and calcium-sensing receptor in highly proliferative parathyroid adenomas.

OBJECTIVE: A significant decrease in vitamin D receptor (VDR) and calcium-sensing receptor (CaSR) protein expression has been demonstrated recently in parathyroid (PT) adenomas. In this study, we investigated the relationships between the proliferative activity of parathyroid glands (PTGs) and the expression of VDR as well as CaSR, and compared it with the clinical severity in patients with primary hyperparathyroidism (1 degrees HPT). DESIGN: Seven patients with 1 degrees HPT were included in this study. Four patients with thyroid carcinoma served as controls. METHODS: Immunohistochemical staining was performed on serial sections of PTGs with specific antibodies against CaSR, VDR, and Ki67. Areas examined in each section were selected at random in relation to the gland size. The number of Ki67-positive cells was expressed as a labeling index (LI; positive cells per 1000 PT cells). The expression of CaSR and VDR was semi-quantitatively analyzed based on the intensity of staining. After averages of the scores from all areas were calculated, CaSR and VDR scores, and Ki67 LI were assigned to each gland for use in statistical analyses. RESULTS: In PT adenomas, scores of VDR and CaSR were markedly lower than in normal PTGs (P<0.01), while the proportion of Ki67-positive cells in PT adenomas was significantly higher than in normal PTGs (P<0.01). Single regression analyses revealed that Ki67 LI was positively correlated with serum levels of intact parathyroid hormone and Ca, and PTG weight (R=0.70, P<0.05, R=0.78, P<0.01 and R=0.84, P<0.05 respectively). Ki67 LI was negatively correlated with CaSR and VDR scores (R=-0.78, P<0.01 and R=-0.72, P<0.05 respectively). Moreover, there was a strong positive relationship between CaSR and VDR expression (R=0.95, P<0.001). CONCLUSIONS: Marked decreases in VDR and CaSR expression could, at least in part, be responsible for the high proliferation of PT cells and the pathological progression of 1 degree HPT.

Adenoma↗
PubMed2002

Pleural gas gangrene secondary to esophageal injury by an ingested fish bone.

We report a 73-year-old woman with right pleural gas gangrene, treated successfully by thoracoscopic debridement. The clinical course and chest computed radiography and thoracoscopy findings suggested that her condition resulted from a relatively rare esophageal injury after she accidentally ingested a fish bone. Video-assisted thoracoscopic intervention has proved useful in cases involving pleural gas gangrene.

Aged↗
PubMed2002

Visualization of conjunctival cyst by indocyanine green.

PURPOSE: To report complete removal of conjunctival cyst using indocyanine green solution to facilitate visualization. DESIGN: Interventional case report. METHODS: A 71-year-old woman referred with the diagnosis of severe conjunctival chemosis of her right eye of several months' duration was found to have a large conjunctival cyst. After informed consent was obtained, surgical resection of the cyst was performed. RESULTS: Under topical anesthesia, indocyanine green solution was injected through a 27-gauge needle into the conjunctival cyst. This achieved excellent visualization of the cyst outline and facilitated complete resection. During the resection, staining of the cyst wall remained despite a small perforation in the capsule, and complete resection was achieved without difficulty. CONCLUSION: Injection of indocyanine green solution into a conjunctival cyst may be used to facilitate visualization and aid in complete resection of the cyst wall.

Aged↗
PubMed2002

Morphometric analysis of liver macrophages in patients with colorectal liver metastasis.

Kupffer cells, residential liver macrophages, have binding sites for carcinoembryonic antigen (CEA), but their role in metastatic liver tumor progression has not been well addressed clinically. Liver macrophages were analyzed morphometrically and their relationship with CEA and tumor microvessel density (MVD) was examined in 71 patients who underwent macroscopic curative hepatectomy for metastatic liver tumors from colorectal cancer. In paraffin-embedded sections, MVD was evaluated by CD34-positive cell counts, liver macrophages visualized using anti PG-M1 (CD68) antibody were analyzed, and membrane-bound CEA was assessed by immunoreactivity of tumor cells for CEA. The area of liver macrophages in peritumoral regions (43.0 +/- 11.6 microm2) was significantly larger than that in non-tumor regions (25.2 +/- 24.2 microm2) (P < 0.0001). The liver macrophage density in peritumoral regions was 154 +/- 49 per field, and was significantly higher than in non-tumor regions (74 +/- 24 per field) (P < 0.001). The density and the area of liver macrophages had no correlation with serum CEA levels and the degree of tumor CEA expression. A weak positive correlation was observed between MVD and liver macrophage density (P = 0.0104, Spearman rank correlation coefficient = 0.31). Cox multivariate regression analysis showed that MVD greater than 50 (P = 0.0233, hazard ratio = 2.463), and the area of liver macrophages larger than 40.9 microm2 (P = 0.0485, hazard ratio = 2.127), were significant independent prognostic factors. The present morphometric analysis suggests that the liver macrophages are accumulated and activated in peritumoral regions in patients with colorectal liver metastasis and this accumulation and activation of liver macrophages, with which soluble or membrane-bound CEA might not be associated, are related with patients' poor prognosis.

Adult↗
PubMed2002

In vitro evaluation of dextran sulfate cellulose beads for whole blood infusion low-density lipoprotein-hemoperfusion.

We describe results from a feasibility study of a newly developed low-density lipoprotein (LDL) adsorbent designed for use in whole-blood infusion LDL-hemoperfusion. The adsorbent has almost the same chemical structure as the Liposorber adsorbent (dextran sulfate cellulose beads) but has a larger particle size. In whole-blood perfusion tests, the adsorbent adsorbed atherogenic LDL cholesterol directly from whole blood but left concentrations of high-density lipoprotein cholesterol largely unchanged. In whole-blood perfusion tests using fresh human donor blood or bovine blood anticoagulated with acid citrate dextrose solution or sodium citrate, the adsorbent showed minimal side effects in terms of blood cell activation, complement activation, and blood cell loss, suggesting that it has excellent blood compatibility. In addition, the adsorbent showed mechanical stability and absence of hemolysis. In conclusion, the new adsorbent showed the appropriate characteristics for an LDL adsorbent column for use in whole-blood infusion LDL-hemoperfusion.

Adsorption↗
PubMed2002

Detection of measles virus genomic RNA in tear samples from a patient with measles keratitis.

PURPOSE: To report a case of measles keratitis, in which measles virus genomic RNA was detected in tear samples. METHODS: Samples of tears and pharyngeal mucus were obtained from a 19-year-old man with active systemic measles on day 7 after illness onset. These specimens were then subjected to reverse-transcriptase polymerase chain reaction (RT-PCR), using measles-specific primers. RESULTS: One week after systemic measles outbreak, the patient presented with a chief complaint of irritation in both eyes. Slit-lamp examination revealed bilateral superficial punctate keratopathy in the central cornea with small diffuse subepithelial infiltrations, and RT-PCR detected measles virus genomic RNA in tears and pharyngeal mucus. The patient was treated with topical 0.1% fluorometholone and 0.5% levofloxacin three times a day for 1 week, and the keratopathy resolved without sequelae. CONCLUSION: This report demonstrates for the first time the presence of measles virus genomic RNA in the tears of a patient with measles keratitis. It also highlights the utility of RT-PCR for rapid detection of measles RNA in tear or mucus samples. Furthermore, the presence of virus in bodily fluids and secretions signifies the potential contagiousness of this type of keratopathy.

Adult↗
PubMed2002

Silencing of the tapetum-specific zinc finger gene TAZ1 causes premature degeneration of tapetum and pollen abortion in petunia.

TAZ1 (TAPETUM DEVELOPMENT ZINC FINGER PROTEIN1; renamed from PEThy; ZPT3-2) cDNA was first isolated as an anther-specific cDNA from petunia. Here, we report a functional characterization that includes analysis of spatial and temporal expression profiles and examination of anther phenotypes in TAZ1-silenced plants. TAZ1 showed a biphasic expression pattern. In the premeiotic phase, TAZ1 transcripts were found to accumulate in all cell types of the anther except the tapetum and gametophytic tissues, whereas the postmeiotic phase of anther development was characterized by expression exclusively in the tapetum. Silencing of TAZ1 by cosuppression resulted in aberrant development and precocious degeneration of the tapetum, followed by extensive microspore abortion that started soon after their release from pollen tetrads. A few pollen grains that survived showed reduced flavonol accumulation, defects in pollen wall formation, and poor germination rates. This study demonstrates an essential role for TAZ1 in the postmeiotic phase of tapetum development.

Cell Survival↗
PubMed2002

Irregularity of parenchymal echo patterns of liver analyzed with a neural network and risk of hepatocellular carcinoma in liver cirrhosis.

OBJECTIVE: In this study, we scored the hepatic parenchymal echo patterns as the coarse score (CS) analyzed with a neural network in cirrhosis patients and calculated the variations in CS as the coefficient of variation, and evaluate their usefulness as predictor of the development of hepatocellular carcinoma (HCC). METHODS: The relationship between the degree of variation in CS and histopathological findings was assessed in 10 autopsied livers fixed in formalin. The degree of intrahepatic variation in CS was calculated as the coefficient of variation of CS (CVCS). Irregular regeneration of liver cells in autopsied livers was classified into two categories, slight and severe. A total of 56 cirrhosis patients were prospectively followed to evaluate the predictors of HCC. RESULTS: A significant positive correlation was observed between CVCS and the coefficient of variation of the diameter of the regenerative nodules. Coefficient variation of nodule diameter and CVCS in patients in whom irregular regeneration was severe were significantly higher than those in patients in whom irregular regeneration was mild (p < 0.05). Concerning the relationship between hepatitis virus markers and CS or CVCS, CVCS was significantly higher in those who were hepatitis C virus antibody positive and those who were hepatitis B surface antigen negative (p < 0.01). Using a combination of CS and CVCS, the incidence of HCC, as determined by the Kaplan-Meier method, was significantly higher in patients whose CS was > or = 1.5 and CVCS was > or = 15%, as compared with that in patients whose CS was <1.5 and CVCS was <15% (p < 0.01) and whose CS was > or = 1.5 and CVCS was <15% (p < 0.05). Multivariate analysis of the predictors for HCC using the Cox's proportional hazards model showed a significant correlation between the risk of development of HCC and CVCS, CS and serum alpha-fetoprotein level. CONCLUSIONS: CVCS and CS can be calculated from liver echo patterns and are useful for identifying a high-risk group for HCC.

Alanine Transaminase↗
PubMed2002

Changes in retinal synaptic proteins in the transgenic model expressing a mutant HRG4 (UNC119).

PURPOSE: HRG4 (UNC119) is a photoreceptor synaptic protein, a truncation mutant of which has been shown to cause late-onset cone-rod dystrophy in a patient and retinal degeneration with marked synaptic degeneration in a transgenic model. To investigate the mechanism of the retinal degeneration, the effect of the mutant protein expression on the other synaptic proteins was examined. METHODS: The status of 12 known synaptic proteins in the retinas of 5-month- and 13-month-old HRG4 transgenic and control mice was examined by Western blot analysis. Three selected proteins were analyzed by immunofluorescence in the 13-month-old retinas. The 12 proteins were tested for binding to HRG4 by a direct-binding assay and Western blot analysis. RESULTS: A decrease in three synaptic vesicle proteins and an increase in five cytoplasmic and plasma membrane proteins was detected by Western blot analysis in the older but not the younger transgenic retinas. These changes were demonstrated in both the outer and inner plexiform layers of the retina by immunofluorescence, along with a significant reduction in the thickness of the inner plexiform layer. A 23-kDa specie was found to bind to HRG4, but none of the 12 synaptic proteins matched it, according to immunoblot analysis. CONCLUSIONS: The expression of a mutant HRG4 protein in the photoreceptor synapses of the transgenic model had an intrasynaptic and transsynaptic effect, resulting in a decrease in three synaptic vesicle proteins, an increase in five cytoplasmic and plasma membrane proteins, and a significant reduction in the thickness of the inner plexiform layer. These changes were age dependent, similar to the pathologic phenotype of the transgenic model and the patient, and supported a close relationship of HRG4 with other participants in synaptic vesicle function. This interaction was not mediated by a direct coupling of HRG4 with any of the tested synaptic proteins but possibly through interaction with a 23-kDa protein.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Immunoreactive Characteristics and Classification of Hyperparathyroidism.

Hyperparathyroidism is caused mainly by three different conditions: namely, secondary hyperplasia, primary hyperplasia, and adenoma with only a few cases due to carcinomas. Histological distinction among these diseases is still difficult. In an attempt to characterize the three conditions, 17 cases from patients with hyperparathyroidism and 12 with normal glands were investigated immunohistochemically using antibodies against PTH, PTHrP, Ki-67 (MIB-1), and chromogranin A. The normal glands showed a diffuse staining pattern for PTH, and focal staining for PTHrP and for chromogranin A. Secondary hyperplasia demonstrated either focal, diffuse, or mixed staining in one gland with the three antibodies. For the primary hyperplasias and adenomas, the cases could be divided into two groups. The first group (group I), including 1 case of primary hyperplasia and 3 cases of adenoma, showed a homogeneous staining pattern with all three antibodies. A heterogeneous staining pattern similar to secondary hyperplasia was found in the other 8 cases that formed the second group (group II). There were five types of cytologic staining patterns after immunostaining. In secondary hyperplasia and group II, several patterns appeared simultaneously. On the contrary, only one pattern was found in group I. The proliferative index (P1) from Ki-67 staining of group I was also significantly higher than in group II. A lower P1 was observed in the normal glands. The present results indicate that different immunohistochemical characteristics exist in primary hyperplasias and in adenomas.

Journal Article↗