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Biomedical subjects

Y Akagi

Publications and source records attributed to Y Akagi.

156 records · Page 9Linked to original sources
PubMedDate not supplied

Histologic examination of dislocated lenses.

PURPOSE: To examine histological changes resulting from dislocated and subluxated lenses. CASES: The subjects consisted of 16 patients (aged 52-89 years) who underwent total lens extraction for lens dislocation or subluxation in the Department of Ophthalmology at Fukui Medical University during the period between April 1991 and June 1998. There were 5 patients (6 eyes) with traumatic dislocation and 11 patients (11 eyes) with idiopathic dislocation. RESULT: Rupture of the cortical fibers and migration of the epithelial cells toward the posterior pole of the lens were more frequently noted in patients with traumatic dislocation than in the idiopathic group, and both findings were often simultaneously observed. Rupture of the cortical fibers was considered attributable to external pressure transmitted to the lens. CONCLUSION: We speculate that the concurrent migration and dislocation of the equatorial bow architecture toward the posterior pole was caused by inhibition of differentiation of the epithelial cells to fiber cells by external pressure on the equatorial region.

Aged↗
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Immunohistochemical study of apoptosis of lens epithelial cells in human and diabetic rat cataracts.

PURPOSE: To evaluate apoptosis of lens epithelial cells by immunohistochemical methods. METHODS: We performed terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assays on capsulotomy specimens (53 patients, 68 eyes) from patients who had undergone cataract surgery, and on the epithelium of diabetic cataracts in rats (72 rats, 144 eyes). An animal model of diabetic cataracts was prepared by injection of streptozotocin in 3-week-old rats. The specimens of rats were also examined using the proliferating cell nuclear antigen (PCNA) immunohistochemical staining method. RESULTS: Although some TUNEL-positive cells were detected in capsulotomy specimens, we recognized little correlation between their distribution and the morphological classification of the cataracts. In the animal model of diabetic cataracts, TUNEL-positive cells were seen around the regions of accumulated epithelial cells. In the accumulated regions, PCNA-labeled cells undergoing DNA synthesis were also detected. CONCLUSIONS: These results suggest the possibility that apoptosis occurs in human lens epithelial cells. Apoptosis and proliferation of lens epithelial cells may be induced by factors such as hyperglycemia.

Aged↗
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Histology of anterior capsule edges produced by CCC and DC.

We compared the postoperative characteristics of the anterior capsule edges produced by two incision techniques: continuous curvilinear capsulorhexis (CCC) and diathermy capsulorhexis (DC). We examined the incised rims of human and animal capsules histologically and also compared the configuration and strength of the rims produced in animal experimentation. Histological examination of rabbit lenses revealed that 0.5 seconds was sufficient for coagulation of the anterior capsule: longer times caused deeper cortical tissue damage. Experimentally produced small capsulorhexis (3.5 mm diameter) with DC produced edges were less elastic than with CCC when tension was applied.

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Possible prognostic markers in conjunctival dysplasia and squamous cell carcinoma.

Conjunctival squamous cell carcinoma (SCC) can develop from carcinoma in situ or severe dysplasia known as conjunctival intraepithelial neoplasia (CIN). Conjunctival intraepithelial neoplasia and SCC are histopathologically well-defined conditions. However, it is difficult to determine the grading of dysplasia by clinical morphologic findings. Recently, proliferating cell nuclear antigen (PCNA) immunostaining, p53 immunostaining, and argyrophilic nucleolar organizer regions (AgNORs) staining have been established as valuable means of studying the biologic behavior of malignant cells. In the present study, these three staining techniques were used to examine histologic preparations of three conjunctival dysplasia and one SCC lesion. Five conjunctival tumor samples were obtained from four patients between July 1993 and October 1995. Following formalin fixation and embedding in paraffin, PCNA, and p53 immunostaining and AgNORs staining was performed with all tissue specimens. The PCNA-positive rate was the highest in SCC, followed by severe dysplasia and mild dysplasia. The p53-positive rate was the highest in severe dysplasia, followed by mild dysplasia, and negative in SCC. The AgNORs-count increased as malignancy advanced. These staining methods, which are markers for proliferative potency and cell differentiation, will be useful for early detection of changes in malignancy and will aid in decisions on treatment and prognosis.

Aged↗
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Postoperative changes over time in size of anterior capsulorrhexis in phacoemulsification/aspiration.

In the present study, we attempted to determine the extent to which an anterior capsulorrhexis carried out during cataract surgery contracts postoperatively. The size of the continuous curvilinear capsulorrhexis (CCC) was measured at the end of surgery and at the final follow-up examination in 52 eyes of 40 patients who underwent phacoemulsification/aspiration and implantation of an intraocular lens (IOL) with 6-mm optics. Images obtained by video during surgery and by slit-lamp microscopy were used to determine the CCC size with reference to the optics of the IOL. The average CCC size was 5.0 mm at the end of surgery; it contracted to 4.4 mm by the final postoperative examination. The contraction of the anterior capsule progressed rapidly in the first 50 days following surgery and then gradually thereafter. The extent of contraction was greater in older patients. The smaller the CCC size immediately after surgery, the more rapidly it contracted. The size of the capsulorrhexis contracted an average of 22% following cataract surgery. The contraction rate tended to be higher in older patients. The results suggest that the capsulorrhexis carried out in cataract surgery for elderly patients should be sufficiently large, but not larger than the optics size of the IOL.

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Analysis of changes in corneal shape and refraction following scleral buckling surgery.

PURPOSE: A prospective study was performed to investigate changes in corneal shape and axial length following scleral buckling surgery. METHODS: We investigated the changes in corneal shape, refraction, and axial length following scleral buckling surgery in 24 patients who underwent local buckling and 14 patients who underwent encircling with additional segmental buckling. The corneal shape was determined by corneal topography and autokeratometry, refraction was measured by autorefractometry, and axial length was measured by A-mode ultrasonography before surgery, and 1, 2, and 7 days, and 1, 3, and 6 months after surgery. RESULTS: After local buckling, the axial length shortened and a hyperopic change was observed. After encircling with additional segmental buckling, the axial length elongated and a myopic shift was detected. The direction of the surgically induced corneal astigmatic vectors was almost identical to the direction of the buckle. There was a tendency for shorter distances between the limbus and the buckle to be associated with greater absolute values. Astigmatism gradually decreased following surgery and stabilized in about 3 months. CONCLUSIONS: Surgeons should select a surgical procedure to ensure favorable postoperative visual acuity while minimizing changes in the shape of the cornea.

Astigmatism↗
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Selective pericyte degeneration in the retinal capillaries of galactose-fed dogs results from apoptosis linked to aldose reductase-catalyzed galactitol accumulation.

Galactose-fed dogs develop retinal capillary changes similar to diabetic retinopathy with pericyte degeneration as the initial lesion. This is followed by the formation of microaneurysms, hemorrhages, and some areas of acellularity. To investigate the mechanisms for selective pericyte degeneration, retinal capillary pericytes and endothelial cells isolated from beagle dog retina were cultured for 2 weeks in Dulbecco's modified Eagle's medium (DMEM) containing 50 mM D-galactose. Apoptosis was detected in pericytes but not endothelial cells by in situ terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick end labelling (TUNEL) staining and the DNA fragmentation assay on agarose gel electrophoresis. This apoptosis was prevented by the addition of the aldose reductase inhibitor AL 1576 to the culture medium containing galactose. Apoptosis was not observed when pericytes were similarly cultured in control DMEM medium. These data support the premise that the selective degeneration of retinal capillary pericytes observed in galactose-fed dogs is linked to increased aldose reductase activity in these cells.

Aldehyde Reductase↗
PubMedDate not supplied

The HVJ liposome method.

Recent advancement of gene technology allows us a practical approach to gene therapy. Among various in vivo gene transfer techniques available, the HVJ liposome method is an efficient procedure which could target the glomerular cells. Using this method, HVJ-mediated cell fusion activity enables us to introduce genetic materials directly into the cytosol without degradation. In addition, cointroduction of non-histone nuclear protein, high-mobility group (HMG-1), efficiently facilitates migration of foreign DNA to the nucleus. Although there still exist some limitations, the HVJ liposome method may be applicable to the treatment of glomerular diseases as well as to analysis of the molecular aspects of renal pathophysiology.

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Glowing podocytes in living mouse: transgenic mouse carrying a podocyte-specific promoter.

Green fluorescence protein (GFP) has been utilized as a marker of gene expression due to the great advantage in its simple and quick detectability. We generated transgenic mice carrying a GFP cDNA under the control of a beta-actin/beta-globin promoter (CX promoter) and cytomegalovirus enhancer. The green luminescence derived from GFP was apparent in skeletal muscle, pancreas, heart and kidney, but not in other tissues. The GFP expression in the kidney was localized in podocytes. Moreover, in situ hybridization of GFP showed that the transcriptional level was highly active in the podocytes. These results suggested that the glowing green fluorescence would be a useful in vivo marker of podocyte in these transgenic lines in the physiological and pathophysiological state, and that the CX promoter could allow a podocyte-specific expression of a molecule of interest in kidney.

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A novel strategy for remission induction and maintenance in cancer therapy.

The p53 tumor suppressor gene plays an important role in protecting cells from developing undesirable proliferation. The mutant p53 gene or malfunctioning p53 protein found in more than 50% of cancer cells impedes DNA repair or apoptosis induction. This may be why some cancers gain resistance to chemotherapy and radiation and become more resistant after frequent cancer treatments. A non-toxic p53 gene activator would induce cancer cell apoptosis and help damaged cancer cells to recover. Therefore, the combination use of chemotherapeutics or radiation with a non-toxic p53 gene activator will be crucial in cancer therapy, damaging DNA with chemotherapeutics or radiation on the one hand and promoting apoptosis induction with p53 gene activator on the other. This strategy would be most efficient for remission induction and maintenance in cancer therapy. Antineoplastons are naturally occurring peptides and amino acid derivatives that control neoplastic growth. Antineoplaston A10 and AS2-1 are chemically identified and synthesized antineoplastons proven to inhibit cancer cell growth by arresting the cell cycle in the G1 phase and inhibiting tumor growth by reducing mitosis. These agents are thought to be good candidates for clinically easily applicable non-toxic p53 gene activators. Our cases of advanced cancer responded well to combination treatment using chemotherapeutics and irradiation with antineoplaston A10 and AS2-1 in clinical trials being conducted in Kurume University Hospital. We describe herein the clinical cases and discuss the possible mechanism of action of this combination therapy.

Adult↗
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Gene transfer and kidney disease.

There is little doubt that molecular biological intervention therapy has come of age and its potential is arousing tremendous excitement. A gene transfer technique, the HVJ-liposome method, is now applicable as a tool for the dissection of molecular aspects in the pathophysiology of renal diseases, and for gene therapy in experimental glomerulonephritis. Overexpressed transforming growth factor (TGF)-beta in the normal rat glomeruli, by gene transfer of TGF-beta cDNA, leads to glomerulosclerosis. However, inhibition of the TGF-beta action by antisense oligonucleotides can suppress the development of the experimental glomerulonephritis. We investigated whether in vivo gene transfer of chimeric proteins, composed of the extracellular domain of TGF-beta type II receptor fused with IgC-Fc, suppresses experimental glomerulonephritis. The expression of TGF-beta in glomeruli was suppressed and so was the extracellular matrix expansion. Taken together with clinical observation of up-regulation of TGF-beta in various glomerulopathies, the dys-regulation of the TGF-beta is important in the development of glomerulosclerosis, and manipulation of this overexpression may prove a novel therapeutic approach for slowing the progression of the disease.

Gene Transfer Techniques↗