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Biomedical subjects

K Tsubota

Publications and source records attributed to K Tsubota.

At least 19 recordsLinked to original sources

Foregut cyst of the oesophageal wall in a cynomolgus monkey (Macaca fascicularis).

Congenital oesophageal cysts of foregut origin are rare in animals and human beings. This report describes a case in a 4-year-old cynomolgus monkey with no clinical symptoms. The cyst, which was located within the oesophageal submucosal tissue near the mid-point of the oesophagus, was lined with pseudostratified ciliated epithelium and had a thin layer of submucosal tissue. The cyst was surrounded by a smooth muscle layer which was partly intermingled with the circular muscle layer of the oesophagus. The muscularis mucosae of the oesophagus was not shared with the cyst wall. Simple tubular glands were present, opening into the cyst lumen. No communication between the cyst lumen and the oesophagus was observed. Cartilaginous tissue, which is a diagnostic feature of bronchogenic cysts, was not identified in the cyst wall. On the basis of the histopathological features, a foregut cyst of the oesophagus was diagnosed.

Animals↗

Microkeratome assisted deep lamellar keratoprosthesis.

AIMS: To establish a keratoprosthesis (Kpro) surgical technique that maintains an intact superficial corneal layer. METHODS: A manual microkeratome (Moria LSK-1) was used to create a 130 mum flap of approximately 10 mm diameter in the right eye of Japanese white rabbits. The stoma beneath the flap area was dissected before the removal of a 5.0 mm stromal disc. A 5.0 mm collagen I immobilised poly(vinyl alcohol) (COL-PVA) disc was placed on the exposed posterior stroma close to Descemet's membrane. The flap was repositioned and fixed using 10-0 nylon sutures, which were removed 2 days following surgery. The corneas were followed clinically by slit lamp microscopy and photographs. Rabbits were sacrificed after 6 months, and the transplanted corneas were examined histologically by haematoxylin and eosin staining and immunohistochemistry against vimentin and alpha-smooth muscle actin (alpha-SMA). RESULTS: The transplanted COL-PVA discs remained transparent throughout the study, with no complications related to the flap or overlying epithelium. The interface between COL-PVA and Descemet's membrane remained clear without signs of opacification caused by scarring or cellular deposition. Pathology revealed the intact COL-PVA polymer in the posterior stroma, with minimal cellular infiltration along the anterior and posterior interfaces. Immunohistology shows vimentin and alpha-SMA staining at levels comparable to lamellar keratoplasty control. CONCLUSIONS: Microkeratome assisted deep lamellar keratoprosthesis may be a safe technique for the transplantation of artificial hydrogels for therapeutic purposes.

Animals↗

Elucidation of apoptosis induced by serum deprivation in cultured conjunctival epithelial cells.

BACKGROUND/AIMS: The conjunctival epithelial cell line, CCL20.2 (CCL), requires the presence of 10% fetal calf serum (FCS) in the medium to survive. To elucidate the molecular mechanism underlying such cell death, including the death signal for these cells, the activities of several caspases in the CCL were measured, and the effects of caspase inhibitors and serum components on cell death were examined. METHODS: CCL was grown in Medium 199 containing 10% FCS, and the medium was changed to Medium 199 with or without 10% FCS, or medium without 10% FCS but containing caspase inhibitors or serum components. After 24 hours' incubation, the enzyme activities of caspases 1, 3, 8, and 9 in the culture supernatants were measured, and the effects of caspase inhibitors and serum components-for example, growth factors, lactoferrin, retinoic acid, were investigated. RESULTS: DNA fragmentation was induced by serum deprivation, confirming that serum deprivation induces apoptosis in CCL. While the activities of caspases 3 and 8 were found to be increased, those of caspases 1 and 9 were not detected in the apoptotic cells. Z-VAD completely suppressed the caspase 3 activation, and specific inhibitors of caspases 1, 8, and 9 partially suppressed the activation. Serum deprivation induced a decrease in the cellular viability, which, however, partially recovered in the presence of caspase inhibitors, epidermal growth factor and retinoic acid. CONCLUSION: These results suggest that the apoptosis induced by serum deprivation involves caspases 1, 3, 8, and 9, and is suppressed by caspase inhibitors. EGF and retinoic acid have a key role in the maintenance of the ocular surface.

Apoptosis↗

Alterations of the ocular surface epithelial mucins 1, 2, 4 and the tear functions in patients with atopic keratoconjunctivitis.

BACKGROUND: An increased understanding of the ocular surface alterations at the cellular level in the conjunctiva and the cornea, may help explain the pathogenesis and the subsequent clinical appearance of atopic ocular allergies, which may be potentially blinding. PURPOSE: To investigate MUC 1, 2 and 4 alterations, tear function and the ocular surface disorder in patients with atopic keratoconjunctivitis. METHODS: Twenty-eight eyes of 14 atopic keratoconjunctivitis patients as well as 22 eyes of 11 age-and sex-matched normal subjects were studied. The subjects underwent corneal sensitivity measurements, Schirmer's test, tear film break-up time (BUT), fluorescein and Rose Bengal staining of the ocular surface, conjunctival impression cytology and brush cytology. Impression cytology samples underwent periodic acid-Schiff and immunohistochemical staining with MUC 1, 2 and 4 antibodies. Brush cytology specimens underwent evaluation for inflammatory cell numbers and quantitative real-time-PCR for MUC 1, 2 and 4 mRNA expression. Patient eyes with fluorescein and Rose Bengal scores greater than four points were regarded to have significant epithelial disease in this study. RESULTS: The mean corneal sensitivity and BUT values were significantly lower in atopic patients with significant epithelial disease, compared with patients with insignificant epithelial disease and controls (P < 0.01). Brush cytology specimens from patients with significant epithelial disease revealed significantly higher numbers of inflammatory cells (P < 0.01). Specimens from patient eyes showed positive staining for MUC 1, 2 and 4. MUC 1, 2 and 4 mRNA expressions were significantly higher in eyes with significant epithelial disease compared with eyes with insignificant epithelial disease and eyes of control subjects. CONCLUSION: Ocular surface inflammation, decline in corneal sensitivity, tear film instability, changes in conjunctival epithelial MUC 1, 2 and 4 mRNA expressions were thought to be important in the pathogenesis of atopic ocular surface disease.

Adolescent↗

Preliminary repair of eyelids for the treatment of opaque corneas caused by burns.

The treatment of opaque cornea as a result of a burn is challenging, because the cornea often re-opacifies even after transplantation. One of the main risk factors is the deformity of the eyelids, and we have developed a new treatment for this. Preliminary repair of the lower eyelid is done by an auricular composite graft before transplantation, so that the grafted materials can be safely protected by the eyelids. The results of treatment since have greatly improved. Preliminary repair of the eyelid is an effective way to secure successful transplantation.

Adolescent↗

Transplantation of corneal endothelium with Descemet's membrane using a hyroxyethyl methacrylate polymer as a carrier.

AIMS: To evaluate the histology and function of Descemet's membrane transplanted with intact endothelium. METHODS: Japanese white rabbits and human eyebank eyes were used as donors and recipients of Descemet's membrane transplantation. Donor endothelium was hydrodissected by injecting indocyanine green from a limbal incision, and then processed as a corneal scleral button. A 6 mm diameter donor sheet was trephined, and folded in half using a 6 mm diameter polymer as a carrier. Recipient endothelium was also hydrodissected from the limbus using trypan blue to stain the Descemet's membrane. Continuous curvilinear descemetorhexis (CCD) was performed to remove a circular section of the Descemet's membrane using a 27 gauge cystotome. Donor tissue was inserted into the anterior chamber through a 5 mm limbal incision and apposed to the host stroma. Polymers were removed following transplantation. Similar surgical procedures were performed in both rabbits and eyebank eyes. Haematoxylin eosin stains were performed after 28 days in rabbits, and eyebank eyes were fixed immediately following surgery for endothelial cell counts. RESULTS: Rabbit control eyes demonstrated stromal oedema caused by loss of Descemet's membrane, whereas transplanted eyes had clear corneas. The mean (standard deviation) pachymetry of operated eyes was 376.6 (SD 32.5) mum compared with 389.6 (SD 25.1) mum in the unoperated eye. Mean endothelial density immediately following surgery in eyebank eyes was 2749 (SD 288) cells/mm(2). CONCLUSIONS: Transplantation of Descemet's membrane by CCD produces a functional graft with an optically clear interface similar to control cornea.

Animals↗

Decreased tear lipocalin concentration in patients with meibomian gland dysfunction.

BACKGROUND/AIM: Recent studies have demonstrated that tear lipocalin (TL) and phospholipids have a crucial role in maintaining tear film stability. The level of TL in patients with meibomian gland dysfunction (MGD) was examined and these data were correlated with the severity of their clinical disorder. METHODS: 12 patients with obstructive MGD, 12 patients with seborrhoeic MGD, and 12 age matched normal control subjects participated in this study. 3 mul of unstimulated tears were collected with a micropipette from the inferior tear meniscus in the right eye of all subjects. Tear samples were fractionated by high performance liquid chromatography, and TL concentrations were assayed with a bicinchoninic acid technique. RESULTS: The mean concentration of TL in patients with obstructive and seborrhoeic MGD was significantly lower than in normal controls. TL concentration correlated positively with tear film break up time and negatively with fluorescein staining scores. CONCLUSION: These results suggest that TL deficiency may be a predisposing factor for the manifestation of symptoms in MGD.

Aged↗

Development of a wearable computer system with a hands-free operation interface for the use of home health caregiver.

We previously developed a network-based medical care support system called the Hyper Hospital, a computer network with an interface that is dedicated to patient care. In this study, we developed a wearable information system that is designed so that a caregiver can obtain information and control various support devices within the home-care environment. In our system, the wearable computer itself consists of a computer network built into a jacket. Each required function is implemented by a dedicated small computer connected to the in-jacket network. A new function may easily be added to the system by connecting additional computers. A network comprising such a set of single-function computers becomes a highly efficient information system when applied to health care support.

Caregivers↗

Salivary flow and its relationship to oral signs and symptoms in patients with dry eyes.

OBJECTIVES: The aim of this study was to investigate oral symptoms and clinical parameters in dry eye patients. Subjective reports of the sensation of a dry mouth, salivary flow rates, and clinical parameters of oral disease related to three different types of dry eye patients were examined. SUBJECTS AND METHODS: There were 224 individuals, including dry eye patients and control subjects. The dry eye patients were classified into three types: patients with Sjögren's syndrome (SS-DE), patients without SS-DE (non-SS-DE), and patients with Stevens-Johnson syndrome (SJS-DE). Salivary flow rates were measured using two kinds of sialometry. Subjective and objective oral symptoms and signs were also examined. RESULTS AND CONCLUSION: Over half of the dry eye patients complained of a dry mouth. The flow rates of their stimulated whole saliva and parotid saliva were significantly lower than those of the control groups (P < 0.05, P < 0.01). The sensation of a dry mouth and changes in oral soft tissues, dental caries, and oral Candida frequently occurred in dry eye patients.

Adult↗

Efficacy of core vitrectomy preceding triple corneal procedure.

AIMS: To evaluate the effectiveness of core vitrectomy preceding triple corneal procedure (penetrating keratoplasty, extracapsular cataract extraction, and intraocular lens (IOL) implantation). METHODS: Thirty one consecutive eyes of 31 patients with indication for triple corneal procedure were randomly assigned to either triple procedure with core vitrectomy (vitrectomy group) or without vitrectomy (control group). The success rate of IOL implantation, IOL positioning, intraoperative and postoperative complications, endothelial cell loss, and best corrected visual acuity (BCVA) were compared. Follow up period was six months. Factors that may contribute to vitreous pressure elevation were also investigated in each case. RESULTS: There was no statistically significant difference in each clinical parameter examined except a tendency of facilitating IOL implantation (p = 0.11). There were two cases of vitreous loss in the control group. Retinal detachment was not seen in any of the cases. The body mass index and age were related to higher vitreous pressure (p<0.05). CONCLUSION: Core vitrectomy preceding triple corneal procedure is not necessary for all cases.

Aged↗

Inflammatory cells in brush cytology samples correlate with the severity of corneal lesions in atopic keratoconjunctivitis.

BACKGROUND: Inflammatory cells infiltrating to the tarsal conjunctiva are thought to be involved in the pathogenesis of corneal lesions in severe allergic conjunctival diseases. The relation between such cells and the severity of corneal lesions was studied. METHODS: Six patients with atopic keratoconjunctivitis (AKC) were enrolled in this study. Tarsal brush cytology findings and the severity of corneal damage at that point were recorded and analysed for correlation. RESULTS: Four out of six patients exhibited correlation between eosinophils and corneal damage. Three out of six patients exhibited correlation between neutrophils and corneal damage. Two out of six patients exhibited correlation between both eosinophils and neutrophils and corneal damage. Analysis of all data from all patients taken together revealed that both eosinophils and neutrophils in brush cytology samples significantly correlated with corneal damage. CONCLUSIONS: Inflammatory cells in brush cytology samples correlated with corneal damage. Evaluation of the relative percentages of inflammatory cells in brush cytology samples is a useful method of assessing disease activity in allergic conjunctival disease.

Adolescent↗

Autologous serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease.

We investigated the efficacy and safety of autologous serum eye drops for the treatment of severe dry eye after allogeneic haematopoietic stem cell transplantation (SCT). A total of 14 patients (four males and 10 females; median age, 31.0 years) with severe dry eye associated with chronic graft-versus-host disease (cGVHD) were enrolled in this study. All patients were refractory to treatment with conventional artificial tears. Autologous serum eye drops, a solution made of 20% autologous serum in sterile saline, were applied 10 times per eye per day. The patients were evaluated every 4 weeks according to visual acuity, corneal sensitivity, vital staining of the ocular surface, tear dynamics, and subjective assessments of symptoms (complaints scores). The median follow-up period was 19.4 months (range: 4-41 months). After 4 weeks of treatment, significant improvement was observed in both complaint scores (from 33.7+/-12.3 to 23.6+/-10.6 points; P<0.01) and fluorescein scores (from 5.8+/-2.0 to 2.4+/-0.9 points; P<0.005). Significant improvements were observed also in rose-bengal staining and tear break-up time. In seven of the 14 patients, the responses were maintained for 6-41 months (median:19.4+/-8.3 months), while six of the other seven patients required treatment with punctal plugs in addition to autologous serum eye drops. One of these other seven patients developed eczema around the eyelids, after which the treatment was discontinued. No serious adverse events were observed. We conclude that autologous serum eye drops are safe and effective for treating severe dry eye associated with cGVHD and that more efficient control of dry eye may be achieved by the combined use of autologous serum eye drops with punctal plugs.

Adult↗

Albumin as a tear supplement in the treatment of severe dry eye.

AIM: To determine the efficacy of using albumin tear supplements in the treatment of ocular surface disorders as a substitute for serum eye drops. METHODS: The effects of albumin on the viability of serum deprived conjunctival cell were observed in vitro. The ability for albumin to compensate for serum was demonstrated by measuring the activity of the apoptosis related enzyme, caspase-3. In an animal study, corneal erosions were inflicted in 40 Japanese white rabbits. Rabbits were treated with 5% or 10% solutions of human albumin, and the decrease in epithelial defect size was compared with saline control and 0.3% sodium hyaluronate. A clinical case series trial of 5% albumin drops was conducted in nine patients with Sjögren's syndrome with severe dry eye. RESULTS: The addition of albumin to serum deprived conjunctival cells inhibited caspase activity and increased cell viability, showing that albumin can compensate for some of the physiological properties of serum. Corneal erosions in rabbits healed significantly faster (p<0.05) in eyes treated with 10% albumin compared with control and sodium hyaluronate. Patients with Sjögren's syndrome used albumin drops showed statistically significant improvement in fluorescein and rose bengal scores, but not in tear break up time and subjective symptoms. No adverse effects of albumin were observed during the study. CONCLUSIONS: The use of albumin as a protein supplement in artificial tear solutions is a viable approach in the treatment of ocular surface disorders associated with tear deficiency.

Aged↗

Abnormal expression and function of Fas ligand of lacrimal glands and peripheral blood in Sjögren's syndrome patients with enlarged exocrine glands.

The objective of our study was to investigate the possibility of Fas ligand protein abnormalities in certain types of Sjögren's syndrome patients with enlarged exocrine glands. Fas ligand expression by lymphocytes infiltrating the lacrimal glands and by peripheral blood monocytes in Sjögren's syndrome patients with enlarged exocrine glands was assessed immunohistologically and by immunoblotting. Cytotoxicity of peripheral blood monocytes and sensitivity to steroids in Sjögren's syndrome patients with enlarged exocrine glands were studied by functional assay. Minimal Fas ligand expression was detected in the lymphocytes of the lacrimal glands and a decreased level of Fas ligand was found in peripheral blood monocytes as assessed by immunoblotting. Functional assay confirmed the decreased cytotoxicity of lymphocytes in Sjögren's syndrome patients with enlarged exocrine glands, and that it is not affected by anti-Fas ligand antibody. By contrast, the sensitivity of lymphocytes in Sjögren's syndrome patients with enlarged exocrine glands to steroids was increased. These observations suggest that abnormal expression and function of Fas ligand occurs in Sjögren's syndrome patients with enlarged exocrine glands.

Adrenal Cortex Hormones↗

Treatment of non-inflamed obstructive meibomian gland dysfunction by an infrared warm compression device.

AIM: To test the short term efficacy and safety of an infrared warm compression device (IWCD, Eye Hot, Cept Co, Tokyo, Japan) as treatment for non-inflamed meibomian gland dysfunction (MGD). METHODS: 37 subjects with non-inflamed obstructive MGD, with and without aqueous tear deficiency (ATD) dry eye, participated in a prospective non-comparative interventional case series. Symptom scores, face scores, tear evaporation rates, fluorescein and rose bengal vital staining, tear break up time (BUT), Schirmer test, meibomian gland obstruction, and meibography were compared before and after 2 weeks of therapy. RESULTS: In a total of 37 cases, total subjective symptom scores and subjective face scores improved significantly, from 12.3 (SD 5.9) to 8.4 (6.1), and from 7.0 (1.7) to 5.3 (2.0) (both p <0.0001). The results for tear evaporation rates during forced blinking (p = 0.002), fluorescein staining (p = 0.03), rose bengal staining (p = 0.03), BUT (p <0.0001), and meibomian gland orifice obstruction score (p <0.0001) had also improved significantly at the end of the 2 week period of infrared thermotherapy. No complaints and/or complications of the IWCD were reported. CONCLUSION: The IWCD was effective and safe for the treatment of MGD. Improved tear stability associated with release of meibum is a possible mechanism of this treatment.

Adult↗