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Biomedical subjects

S Saika

Publications and source records attributed to S Saika.

At least 55 records · Page 3Linked to original sources

Avascular necrosis of bone--a complication of aggressive therapy for acute lymphoblastic leukemia.

The purpose of the present paper was to report cases of avascular necrosis of bone (AVNB) arising as a complication of chemotherapy for acute lymphoblastic leukemia (ALL). X-rays and 99mtechnicium-MDP bone scans were performed on patients with symptoms of bone pain, whereby five patients out of 850 patients were detected to have avascular necrosis of the femoral head. All had received aggressive chemotherapy with steroids. Two patients were still on therapy for the primary disease. In these patients further chemotherapy was continued without steroids. The median period from diagnosis of ALL to development of AVNB was 29 months. Three patients underwent corrective surgical procedures. To conclude, the data suggest that patients receiving combination chemotherapy, especially those with high cumulative doses, run a risk of developing AVNB. Awareness of this complication is important in order to have an early diagnosis so as to limit disability.

Adolescent↗

Deposition of extracellular matrix on intraocular lenses in rabbits: an immunohistochemical and transmission electron microscopic study.

BACKGROUND: We examined by transmission electron microscopy the accumulation of extracellular matrix on intraocular lenses (IOLs) implanted experimentally into rabbit eyes, and evaluated the immunolocalization of such extracellular matrix components as collagen types I, III, and IV, and cellular fibronectin on these IOLs. METHODS: Phacoemulsification and aspiration of the crystalline lens were performed and an IOL was implanted into the capsular bag of each eye of each of 16 adult albino rabbits under general anesthesia. After up to 12 weeks, the animals were killed and the IOLs were removed. Specimens were processed for transmission electron microscopy or for immunohistochemical detection collagen types I, III, and IV, and cellular fibronectin. RESULTS: Transmission electron microscopy revealed an accumulation of extracellular matrix between the residual anterior lens capsule and the surface of an IOL explanted 4 weeks after surgery. Collagen types I and III and cellular fibronectin were detected immunohistochemically on each IOL in association with cellular deposits. Type IV collagen-immunoreactive matrix was not seen on the optic portion, but was detected on the haptic portion of one of six IOLs examined. CONCLUSION: Each component of the extracellular matrix that is deposited on the IOL supplies scaffolding for the adhesion and proliferation of cells. These components are considered to be produced by cells such as lens epithelial cells and macrophages that adhere to the IOL surface.

Animals↗

Deposition of extracellular matrix on silicone intraocular lens implants in rabbits.

PURPOSE: To examine the deposition of extracellular matrix on silicone intraocular lenses (IOLs) implanted experimentally into rabbit eyes by electron microscopy and to determine the immunolocalization of extracellular matrix components, including collagen types and cellular fibronectin, on these IOLs. METHODS: We performed phacoemulsification and aspiration of the crystalline lens and implanted a foldable silicone IOL in the capsular bag of one eye of each of 26 adult albino rabbits under general anesthesia. After 8 weeks the animals were killed and the eyes were enucleated. The silicone IOLs were processed for electron microscopy and for immunohistochemical detection of collagen types I, III, and IV and cellular fibronectin. RESULTS: Electron microscopy revealed deposition of a presumed cell matrix complex on the optic portion of all silicone IOLs, as well as the adhesion of presumed macrophages and foreign-body giant cells. Cellular deposits showed immunoreactivity for cellular fibronectin. Fibrous or membranous deposits exhibited immunoreactivity for cellular fibronectin and collagen types I and III. A few type IV collagen-immunoreactive deposits were also seen. CONCLUSION: Deposits of extracellular matrix components were observed on silicone IOLs. These deposits may form the scaffolding for the adhesion and proliferation of cells. These matrix components appeared to be the products of cells adhering to the surfaces of IOLs, including lens epithelial cells, macrophages and foreign-body giant cells, indicating that the process of granulation was incomplete.

Animals↗

Cell proliferation on the outer anterior capsule surface after extracapsular lens extraction in rabbits.

PURPOSE: To use light microscopy to evaluate the presence and distribution of cells that proliferate on the outer surface of the anterior capsule after experimental lens extraction in rabbit eyes. SETTING: Research Laboratory, Department of Ophthalmology, Wakayama Medical College, Wakayama, Japan. METHODS: Extracapsular lens extraction, with or without implantation of a poly(methyl methacrylate) intraocular lens, was performed in 10 adult albino rabbits under general anesthesia. Animals were killed 1 month postoperatively. Each eye was embedded in paraffin and examined by light microscopy. RESULTS: A capsular bag composed of the anterior and posterior capsules was observed. Mononuclear cells, presumed to be lens epithelial cells (LECs), had proliferated in the space between the capsules as well as on the outer surface of the anterior capsules, in association with an accumulation of extracellular matrix. CONCLUSION: After lens extraction, LECs migrated to and proliferated on the anterior surface of the anterior capsule.

Animals↗

Light and scanning electron microscopy of rabbit lens capsules with intraocular lenses.

PURPOSE: To examine postoperative changes in the lens capsules of rabbit eyes after phacoemulsification and aspiration of the crystalline lens and implantation of posterior chamber intraocular lenses (IOLs) using light and scanning electron microscopy. SETTING: Research Laboratory, Department of Ophthalmology, Wakayama Medical College, Japan. METHODS: The crystalline lens was emulsified and aspirated and an IOL implanted in the capsular bag or ciliary sulcus of each eye in adult albino rabbits under general anesthesia. Animals were killed after 4 weeks, and the lens capsules were removed. The specimens were observed under phase-contrast microscopy and processed for light and scanning electron microscopy. RESULTS: Phase-contrast microscopy revealed presumed lens epithelial cells (LECs) on the central posterior capsules in association with regenerating lenticular fibers and Elschnig pearls in the peripheral capsules. Scanning electron microscopy showed the accumulation of fibrous extracellular matrix on the surface of the posterior capsule in eyes in which the IOL was implanted in the ciliary sulcus. Deposition of packed material attached to the surface of IOLs and of Soemmering's ring were observed in eyes with in-the-bag IOL fixation. At a higher magnification, a parallel arrangement of lenticular fibers was seen in the regenerated lens structure on posterior capsules. An identical structure was observed under light microscopy. Outgrowth of presumed LECs from residual anterior lens capsules and adhesion of macrophages and giant cells were observed on the IOL surface. CONCLUSION: Two types of postoperative changes were observed in lens capsules after implantation of IOLs: accumulation of fibrous extracellular matrix and newly formed lenticular fibers. These changes are attributed to the proliferation of LECs and can induce posterior capsule opacification after IOL implantation.

Animals↗

In vitro effects of doxorubicin and mitomycin C on human Tenon's capsule fibroblasts.

Doxorubicin is an antiproliferative agent, that also inhibits prolyl 4-hydroxylase in vitro. We evaluated the effects of doxorubicin and mitomycin C (MMC) on the proliferation of human Tenon's capsule fibroblasts and the secretion of type I collagen in these cells to explore the potential use of doxorubicin as an antifibrotic agent after glaucoma filtering surgery. Standard immunoassays were used to determine the concentrations of type I procollagen COOH-terminal peptide (PIP), laminin and vitronectin receptor in conditioned media and cell lysates in the presence or absence of doxorubicin or MMC. The mitotic activity and viability of these cells were also determined. Cellular ultrastructure was evaluated by transmission electron microscopy. Doxorubicin and MMC decreased the cellular viability, the mitotic activity, and the production of the peptides measured. The inhibition of PIP secretion into the culture medium was higher in doxorubicin-treated cultures than in MMC-treated cultures at the tested concentrations (5-100 microM). The decrease in PIP levels in cell lysates was less in doxorubicin-treated culture (25 microM) than in MMC-treated culture (25 microM), suggesting that procollagen synthesis and secretion might be attenuated by doxorubicin. Ultrastructural studies revealed increased numbers of lysosomes in the cytoplasm of doxorubicin-treated cells relative to MMC-treated cells. Doxorubicin and MMC reduced cell viability and inhibited the proliferation and synthesis of PIP, laminin, and vitronectin receptor peptide. Inhibitory effects of doxorubicin on PIP secretion were more potent than those of MMC. Doxorubicin may be useful for inhibiting the fibrotic response at the site of ocular filtering surgery.

Adult↗

Collagen synthesis in lens epithelial cells on capsules containing intraocular lens implants in rabbits: immunolocalization of prolyl 4-hydroxylase.

BACKGROUND: We evaluated ultrastructurally the presence and distribution of lens epithelial cells and extracellular matrix on the posterior capsule after implantation of a silicone or a polymethyl-methacrylate (PMMA) intraocular lens (IOL) in rabbits. The immunolocalization of prolyl 4-hydroxylase, an enzyme involved in procollagen synthesis, was also examined in such cells. METHODS: Anesthetized adult albino rabbits (n = 12) underwent phacoemulsification and aspiration (PEA) of the crystalline lens and implantation of a silicone or a PMMA IOL into the capsular bag of one eye. They were killed by an intravenous overdose of pentobarbital sodium. The lens capsules were processed for transmission electron microscopy and for immunohistochemical detection of the beta-subunit of prolyl 4-hydroxylase. RESULTS: Ultrastructurally, lens epithelial cells on the posterior capsule evidenced an accumulation of collagenous extracellular matrix. Prolyl 4-hydroxylase immunoreactivity was detected in the cytoplasm of cells distributed on the capsules. CONCLUSION: Lens epithelial cells are involved in the production of collagenous matrix on lens capsules after PEA and implantation of IOL, resulting in a fibrotic process of the lens capsule.

Animals↗

Immunolocalization of prolyl 4-hydroxylase in fibroblasts cultured from Tenon's capsule of humans.

BACKGROUND: The excessive accumulation of extracellular matrix (ECM) with the repopulation of fibroblasts may lead to an unsuccessful outcome of glaucoma filtering surgery. We examined the immunolocalization of ECM components and prolyl 4-hydroxylase, an enzyme involved in collagen biosynthesis, in cultured Tenon's capsule fibroblasts (TCFs) of humans to evaluate the production of ECM in the cells. METHODS: We used light microscopy to evaluate the immunolocalization of prolyl 4-hydroxylase and ECM components, collagen types I, III, and IV, cellular fibronectin, and laminin in TCFs. Ultrastructural localization of the enzyme was also evaluated by electron microscopy. RESULTS: Immunoreactivity with monoclonal antibodies against the alpha and beta subunits of the enzyme or with the polyclonal antibody against it was detected in the cytoplasm of the cells in a fine granular pattern, indicating its localization in the endoplasmic reticulum (ER). Immunoreactivity for the enzyme was detected in the cisternae of the ER on electron microscopy. Types I and III collagen reactivities were also observed in the cytoplasm in a fine granular pattern. Type IV collagen reactivity was present diffusely on the cell surface. The distribution of laminin reactivity in the cytoplasm resembled that of types I and III collagen. Cellular fibronectin reactivity was observed in the ECM in a reticular pattern. CONCLUSION: Prolyl 4-hydroxylase was located in the cisternae of the ER. TCFs produced a variety of ECM components in vitro. The results provide insight into the fibrotic process during scar formation at the site of a bleb following filtering surgery.

Aged↗

Effect of fibrostatin C, an inhibitor of prolyl 4-hydroxylase, on collagen secretion by human Tenon's capsule fibroblasts in vitro.

PURPOSE: To investigate the effect of fibrostatin C, a prolyl 4-hydroxylase (PH) inhibitor produced by Streptomyces catenulae subsp. griseospora, on type I collagen secretion by human Tenon's capsule fibroblasts (TCFs) in vitro, as an indication of the potential therapeutic efficacy of this compound in antifibrotic therapy after glaucoma filtering surgery. METHODS: The concentrations of type II procollagen COOH-terminal peptide (PIP) in culture medium or cell lysate were determined by immunoassays. For comparison with its effect on PIP secretion, we determined the effects of the agent on the secretion of other peptides, including laminin, vitronectin receptor, and a metalloproteinase inhibitor. The expression of collagens I and III, fibronectin, and PH by TCFs was examined by immunohistochemistry, and cellular ultrastructure was evaluated by transmission electron microscopy. RESULTS: Fibrostatin C (50 microM) significantly reduced the concentration of PIP in culture medium and increased its concentration in the cell lysate in a dose-dependent manner, but it had no effect on the secretion of other peptides. Cell viability and proliferation were not affected by fibrostatin C. Fibrostatin C also increased the number of cytoplasmic granules immunoreactive with antibodies to collagen I or III, but had no effect on fibronectin or PH immunoreactivity. Ultrastructurally, cisternae of the endoplasmic reticulum were dilated in fibrostatin C-treated TCFs, consistent with the retention of underhydroxylated collagen precursors in this organelle. CONCLUSIONS: Fibrostatin C inhibits the secretion of type I collagen by cultured TCFs. This agent may thus prove therapeutically beneficial for inhibiting the excess fibrosis in the wound of filtering surgery.

Aged↗

Heparin-induced thrombocytopenia in hemodialysis patients.

This study was conducted to determine the incidence of heparin-induced thrombocytopenia (HIT), an important complication in heparin therapy, in 154 hemodialysis patients, with characterization of the subtypes using an enzyme-linked immunosorbent assay. The etiology of the immunologic type of HIT is suggested to involve the binding of a specific antibody for platelet factor 4-heparin complex to platelets and their consequent activation. The 154 consecutive patients were newly treated with hemodialysis due to chronic or acute renal failure between January 1993 and July 1995. Heparin-induced thrombocytopenia was suspected in six patients (3.9%), and its presence was confirmed by platelet aggregation testing. Five of the patients with HIT had anti-platelet factor 4-heparin complex antibody detected by the enzyme-linked immunosorbent assay and were diagnosed with immunologic HIT. The patient who did not have the antibody was thought to have another type of HIT.

Acute Kidney Injury↗

Lens epithelial cell outgrowth and matrix formation on intraocular lenses in rabbit eyes.

PURPOSE: To evaluate the presence and distribution of lens epithelial cells (LECs) and extracellular matrix on intraocular lenses (IOLs) implanted in the capsular bag in rabbit eyes. SETTING: Department of Ophthalmology, Wakayama Medical College, Wakayama, Japan. METHODS: Five adult albino rabbits had phacoemulsification and IOL implantation in both eyes. Two or 11 months later, the animals were killed by intravenous pentobarbital. The IOLs were removed and observed under scanning and transmission electron microscopy. RESULTS: In addition to the macrophages and giant cells on the IOLs, all eyes had a monolayer of flattened cells growing out from the residual anterior lens capsule and a fibrous meshwork of extracellular matrix. Unlike those of a macrophagic origin, these cells had no central cytoplasmic elevation of nuclei and few cell surface microvilli and were considered to be proliferating LECs. CONCLUSION: Lens epithelial cells are involved in the eye's cellular reaction to IOLs and in the formation of extracellular matrix on IOLs. Further study of LEC behavior on IOLs should be done to improve IOL biocompatibility.

Animals↗

Protective effects of human urinary trypsin inhibitor against trypsin-induced relaxation in rat aorta.

OBJECTIVES: To investigate the vasodilatory responses induced by trypsin, and to determine the antitrypsin effects of human urinary trypsin inhibitor on blood vessels. DESIGN: Prospective, randomized, controlled study, with repeated measurements. SETTING: University research laboratory. INTERVENTIONS: The isometric tension of the aortic rings isolated from male Wistar rats was recorded. The vasodilatory responses to varying amounts of trypsin (0.01 to 10 U/mL) were examined under pretreatment with human urinary trypsin inhibitor (1 to 10 U/mL), chicken-egg-white trypsin inhibitor (0.1 to 10 mg/mL), N infinity-nitro-L-arginine (3 x 10(-5) M), and denudation of the endothelium. In addition, with the scanning electron microscopy, the endothelium of aorta was examined under treatment with trypsin alone (10 U/mL), and with trypsin plus human urinary trypsin inhibitor (10 U/mL each).4 MEASUREMENTS AND MAIN RESULTS: The addition of trypsin produced dose-dependent relaxation in aortic rings with an intact endothelium, which was abolished by denudation and treatment with N infinity-Nitro-L-arginine. Pretreatment with human urinary trypsin inhibitor and with chicken-egg-white trypsin inhibitor caused dose-dependent inhibition against trypsin-induced vasorelaxation. On the repeated trials of the response to trypsin, the responses gradually developed tachyphylaxis in control aortic rings, whereas no tachyphylaxis developed in rings pretreated with human urinary trypsin inhibitor (10 U/mL). Scanning electron microscopy demonstrated endothelial disruption in aorta exposed to trypsin alone, whereas the endothelium was intact in strips treated with trypsin plus human urinary trypsin inhibitor. CONCLUSIONS: The data indicate that relaxation induced by trypsin is attributable to nitric oxide released from the endothelium, and that human urinary trypsin inhibitor protects vessels against trypsin-induced endothelial injury. It appears that the clinical antishock effect of human urinary trypsin inhibitor is ascribable in part to its antitrypsin activity on the endothelium of vascular smooth muscle.

Animals↗

Pentoxifylline and pentifylline inhibit proliferation of human Tenon's capsule fibroblasts and production of type-I collagen and laminin in vitro.

After glaucoma filtering surgery, an excessive repopulation of Tenon's capsule fibroblasts (TCFs) with the accumulation of extracellular matrix including collagen types during wound healing may cause scarring of the bleb, resulting in surgical failure. Pentoxifylline (PTX) and pentifylline (PTF), both methylxanthine derivatives, are known to inhibit protein synthesis and proliferation of cells in vitro. We examined the effects of these agents on the proliferation of cultured human TCFs and their production of type-I collagen COOH-terminal peptide (PIP) and laminin to investigate the potential use of the agents as antifibrotic agents after filtering surgery. Both agents inhibited the proliferation of cultured human TCFs and their production of PIP and laminin. The inhibitory effects of PTF on proliferation and production of PIP and laminin were greater than those of PTX. These methylxanthine derivatives may have clinical utility in preventing excessive bleb scarring after glaucoma filtering surgery.

Adult↗

Expression of fos family and jun family proto-oncogenes during corneal epithelial wound healing.

PURPOSE: While transformation of epithelial cells to a motile form is the first step in wound healing of the corneal epithelium, the migratory mechanism in these cells is not fully understood. We studied the expression of proto-oncogene mRNAs: c-fos; c-jun; fos B; jun B; jun D in injured corneal epithelium using in situ hybridization. Moreover, we examined immunolocalization of c-Fos and c-Jun protein products to elucidate the transcriptional activation prior to the onset of migration in corneal epithelium. METHODS: An epithelial defect was made on one cornea of 60 Wistar rats. The affected eye was enucleated immediately (within 5 min) or was allowed to heal for 15, 30, 60, 90, 120 and 180 min. Frozen sections were processed for in situ hybridization with c-fos, c-jun, fos B, jun B and jun D mRNAs or were stained with anti-c-fos and anti-c-jun antibodies. RESULTS: Fifteen min after the epithelial ablation, weak signals for c-fos and c-jun mRNAs were detected in the corneal epithelium surrounding the wound. These signals reached a peak 30 to 60 min after ablation, but were no longer evident at 120 min. Immunoreactivities for these proteins were also detected in the same area at 60 to 120 min after the epithelial ablation. Fos B mRNA was detected in the same region at 30 min after the ablation, and reached its peak after 30 to 60 min, but was no longer evident at 120 min. Jun B mRNA was detected in the epithelium around the defect 60 min after the ablation, later than the other proto-oncogenes, and reached its peak after 90 min. The message for jun D was detected in normal epithelium, and was not affected by wounding. CONCLUSIONS: These findings indicate that transcriptional activation of epithelial cells is initiated in the early phase after epithelial ablation, before the cells start to migrate, and that these proto-oncogene products may play important roles in wound healing in corneal epithelium. The time lag of the peak of expression of these proto-oncogenes in this process.

Animals↗

[Electron microscopic observations on the posterior lens capsule after implantation of a silicone intraocular lens in rabbits].

We performed phacoemulsification and aspiration of the crystalline lens and implanted a silicone intraocular lens in the capsular bag in rabbits. The posterior capsules were then observed under transmission electron microscopy 2 or 4 months after the surgery. Lens epithelial cells proliferated between the posterior capsule and the optic portion of the silicone intraocular lens, accompanied with the accumulation of collagenous extracellular matrix.

Animals↗

Collagen types in healing alkali-burned corneal stroma in rabbits.

We evaluated the change in the type of collagen found during healing in the alkali-burned corneal stroma of rabbits. We estimated the relative proportions of alpha chains in pepsin-solubilized collagen, using sodium dodecylsulfate polyacrylamide gel electrophoresis. Bands of alpha 1(I), alpha 2(I), alpha 1(V), and alpha 1(III) chains stained with Coomassie Blue were separated. The alpha 1(III) and alpha 1(V) chains showed a transient proportional increase in healing corneal stroma in the area exposed to alkali. No significant alterations in collagen alpha chains were detected in peripheral corneal stroma that had not been directly exposed to alkali. Our results suggest that the keratocytes which repopulate the alkali-injured corneal stroma early in healing synthesize a higher proportion of collagen types III and V than type I, and then switch to synthesizing predominantly type I collagen as stromal healing progresses. Collagen types III and V thus appear to be of primary importance in the healing of the corneal stroma.

Animals↗

Effect of lysyl hydroxylase inhibitor, minoxidil, on ultrastructure and behavior of cultured rabbit subconjunctival fibroblasts.

BACKGROUND: Minoxidil is an inhibitor of lysyl hydroxylase, an enzyme involved in collagen production, and decreases collagen production in vitro. We investigated the in vitro effects of minoxidil on behavior such as proliferation and migration of rabbit subconjunctival fibroblasts (SCFs). The ultrastructural effect of the drug on SCFs was also examined. METHODS: Proliferation of SCFs and closure of the defect produced in monolayer cultures in the presence or absence of minoxidil was studied. The ultrastructure of SCFs treated with minoxidil was also examined. RESULTS: Minoxidil inhibited SCF proliferation and the closure of the defect produced in monolayer cell sheets. Ultrastructural observations revealed extensive areas of irregularly dilated endoplasmic reticulum in cells treated with minoxidil, indicating the accumulation of protein, probably underhydroxylated collagen precursors, in the cisternae of endoplasmic reticulum. CONCLUSIONS: The results indicated that minoxidil attenuated cellular activities of SCFs such as proliferation and migration in vitro. The exact mechanism of the inhibitory effects of minoxidil on these cellular activities is unknown. The findings suggest that the drug might help to prevent bleb scarring after glaucoma filtering surgery.

Animals↗

Extracellular matrix on intraocular lenses.

We examined the distribution of extracellular matrix components in the proteinaceous matrix on explanted IOLs using immunohistochemistry to clarify the nature of proteinaceous deposits on the surfaces of IOLs. We examined 15 polymethylmethacrylate (PMMA) IOLs and one silicone IOL explanted from patients. The IOLs were immunostained for cellular fibronectin, types I and IV collagen, and vitronectin. Various amounts of fibronectin, types I and IV collagen, and vitronectin were detected in the extracellular matrix on all IOLs with cellular deposits. Types I and IV collagen and cellular fibronectin were present in the extracellular matrix and were probably the products of cells adhering to the IOLs. Vitronectin in the fibrous extracellular matrix appeared to represent an adsorption material derived from the aqueous humor. These proteinaceous deposits associated with cellular deposits indicate unsuccessful formation of granulation tissue and could influence IOL biocompatibility.

Adult↗