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Biomedical subjects

H Mishima

Publications and source records attributed to H Mishima.

At least 19 recordsLinked to original sources
PubMed1992

Interleukin 6 facilitates corneal epithelial wound closure in vivo.

Rapid corneal epithelial wound healing is essential to the maintenance of clear visual acuity. The cytokine interleukin 6 is thought to participate in the wound-healing process. We investigated the effect of interleukin 6 eye drops on the rate of corneal epithelial wound closure in rabbits in vivo. Recombinant human interleukin 6 in phosphate-buffered saline at concentrations of 0.1, 0.3, or 1 mg/L was administered immediately after the epithelium was débrided with the n-heptyl alcohol treatment and 2, 4, 6, 8, 10, 18, 20, 22, 24, 26, and 28 hours after débridement. The eyes were stained with fluorescein and photographed at baseline and at 7, 10, 18, 21, 24, 27, 30, and 43 hours after débridement. The rate of wound healing was calculated with a linear regression analysis based on the areas of the epithelial defects, which were recorded from hour 10 to hour 30. The mean (+/- SD) healing rate in the control group, which received phosphate-buffered saline alone, was 1.03 +/- 0.15 mm2/h. The administration of interleukin 6 at concentrations of 0.1, 0.3, or 1.0 mg/L increased the healing rate significantly (P less than .001) to 1.27, 1.39, or 1.44 mm2/h, respectively. Our results indicate that the administration of interleukin 6 might have clinical applications in the treatment of persistent corneal epithelial defects.

Alcohols↗
PubMed1992

The signal-induced phospholipid degradation cascade and protein kinase C activation.

Acting in synergy with diacylglycerol, unsaturated free fatty acids such as arachidonic, oleic, linoleic, linolenic and docosahexaenoic acids dramatically activate some members of the protein kinase C family at the basal level of Ca2+ concentration. It is plausible that phospholipase C and phospholipase A2, and possibly phospholipase D as well, are involved in the activation of protein kinase C. Presumably, this enzyme activation is integrated into the signal-induced membrane phospholipid degradation cascade, prolonging the activation of protein kinase C. The sustained activity of this enzyme appears to be of importance for long-term cellular responses such as development of neuronal plasticity and gene activation.

Animals↗
PubMed1992

Interleukin 6 promotes epithelial migration by a fibronectin-dependent mechanism.

We investigated the effect of interleukin 6 (IL-6) on the migration of rabbit corneal epithelium in vitro and on the attachment of dissociated corneal epithelial cells to a fibronectin matrix. When corneal blocks were cultured with IL-6 for 24 hours, the length of the path of epithelial migration over exposed corneal stroma increased significantly (p less than 0.005 at the concentration of 10 ng/ml) in proportion to the concentrations of IL-6 (0.1-10.0 ng/ml). The addition of antiserum against fibronectin or of GRGDSP abolished the stimulatory effect of IL-6 on epithelial migration. When corneal epithelial cells were cultured with various concentrations of IL-6, suspended, and plated on wells coated with fibronectin (10 micrograms/ml), the number of cells attached to the wells increased in a dose-dependent manner. The presence of antibody against fibronectin or of GRGDSP during the attachment assay decreased the number of cells attached to the fibronectin matrix, regardless of the fact that the cells had been cultured with IL-6 or not. IL-6 stimulated the attachment of corneal epithelial cells to collagen type IV and to laminin matrices. However, the presence of GRGDSP did not affect the cell attachment to collagen type IV and to laminin. These findings strongly indicate that IL-6 stimulates epithelial migration in the cornea by a fibronectin-dependent mechanism, presumably the increased expression of fibronectin receptors.

Amino Acid Sequence↗
PubMed1992

A human monoclonal antibody derived from axillary lymph nodes of a breast cancer patient reactive to a sulfated glycolipid.

A human monoclonal antibody, BMMK-33G, was established by a fusion of human B-lymphoblastoid cells, HO-323, with lymphocytes of axillary lymph nodes obtained from a breast cancer patient. High-performance thin-layer chromatography (HPTLC)-immunostaining and enzyme-linked immunosorbent assay (ELISA) revealed that BMMK-33G was interestingly directed to enough sulfatide (Galactosylceramid-I2-sulfate), which is one of the sulfate ester containing glycolipids. By immunohistochemical staining, BMMK-33G intensely reacted to breast cancer, pancreatic cancer and gastric cancer. It also reacted to many normal human tissues including mammary glands, but these stainings were weaker than those for cancer. This report describes BMMK-33G, a human monoclonal antibody against sulfatide which may be very useful for studying not only tumor immunology but also autoimmune diseases.

Antibodies, Monoclonal↗
PubMed1992

Transforming growth factor-beta modulates effects of epidermal growth factor on corneal epithelial cells.

In order to understand the mechanisms that bring about maintenance and restoration of the integrity of corneal epithelium, we investigated independent and combined effects of transforming growth factor-beta (TGF-beta) and epidermal growth factor (EGF) on rabbit corneal epithelial cells in cell and organ culture. Specifically, we determined whether incubation with these factors influenced 1) cellular proliferation, 2) ability of cells to attach to a fibronectin matrix, and 3) the rate of epithelial migration over corneal stroma. Incubation with TGF-beta caused a dose-related decrease in the incorporation of 3H-thymidine by the epithelial cells. EGF increased 3H-thymidine incorporation, but this effect was antagonized by the addition of TGF-beta into the incubation medium. Incubation with EGF increased the numbers of cells that attached to a fibronectin matrix. TGF-beta itself did not affect the number of attached cells but, again, it antagonized the stimulatory effect of EGF. Similarly, when corneal blocks were cultured with EGF, epithelial migration increased in a dose-related manner. TGF-beta itself did not affect epithelial migration at any of the concentrations tested (0.1-10 ng/ml), but it antagonized EGF-stimulated epithelial migration. These findings suggest that the proliferation and the migration of corneal epithelial cells are regulated by different mechanisms, and that TGF-beta serves as a modulator of the effects of EGF.

Animals↗
PubMed1992

Protein kinase C subspecies in rat brain synapses and phosphorylation of growth-associated protein.

Synaptosomes isolated from rat hippocampus contained the alpha- and beta-subspecies of protein kinase C (PKC), but not the gamma-subspecies, whereas postsynaptic pyramidal cells contained all these three subspecies. The PKC enzymes were activated synergistically by diacylglycerol and cis-unsaturated fatty acids including docosahexaenoic acid which is abundant in brain phospholipids. The phosphorylation of a PKC-specific substrate, growth-associated protein (GAP-43), which is associated predominantly with presynaptic membranes, was also protein (GAP-43), which is associated predominantly with presynaptic membranes, was also stimulated by diacylglycerol and cis-unsaturated fatty acids, particularly at the micromolar range of Ca2+ concentrations. The results presented suggest that cis-unsaturated fatty acids together with diacyglycerol may take part in the phosphorylation of GAP-43 in presynaptic membranes presumably by the alpha- or beta-subspecies of PKC even after the Ca2+ concentrations return to the basal level.

Animals↗
PubMed1992

[Oxygen-conserving delivery system].

Three methods for improving oxygen delivery efficiency--transtracheal oxygen therapy (TTO), reservoir cannula, and demand-pulse oxygen delivery--are currently available. We discuss our experiences of TTO and its characteristics compared with the other two methods. Since 1988, we have tried to apply TTO to the candidates for home oxygen therapy (HOT) fulfilling the following criteria: 1) good activity and enthusiasm to daily life, 2) high oxygen flow rate with nasal cannula, 3) complicating nasal disorders such as chronic sinusitis, or 4) suffering complications from nasal cannula therapy. We used a disposable 8-Fr feeding tube for a trnastracheal catheter. Patients were taught to change their catheters themselves every day by simply removing the old and reinserting the new catheter. We have experienced nine patients on HOT with TTO. A half to a third of the flow rate of nasal cannular was required with TTO to achieve an equivalent PaO2 level. In cases with hypercapnea, a persistent significant increase of PaCO2 was not found. We measured arterial blood gases, changing the distance from the tract opening to the catheter tip, and it was suggested that in each case there may be an optimum distance to achieve the highest PaO2 level. Seven cases received TTO for more than 18 months, a mean of 30.2 months (range 19.3-48.9) and HOT for a mean of 26.6 months. They all maintained a high degree of enthusiasm for TTO. Two cases could return to work. Five cases enjoyed active daily lives, such as shopping, going out for recreation, travelling, and attending concerts.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Epidermal growth factor stimulates corneal epithelial cell attachment to fibronectin through a fibronectin receptor system.

Epidermal growth factor (EGF) stimulates corneal epithelial migration in vivo and in vitro. Antibody against fibronectin inhibits this effect in vitro, suggesting that a fibronectin-dependent mechanism in involved. To elucidate the action of EGF, we placed rabbit corneal epithelial cells, preincubated in the absence or presence of EGF (10 ng/ml), into wells coated with fibronectin. After 45 minutes of incubation, the numbers of cells attached to the wells were counted. Preincubation with EGF for 6 hr was not effective, but preincubation for 9 hr significantly increased the numbers of cells attached to the wells. These numbers were not increased further by additional preincubation. When concentrations of EGF were reduced, numbers of attached cells decreased proportionally, but remained significantly higher than the numbers obtained with cells not exposed to EGF. The EGF-stimulated attachment to the fibronectin matrix was inhibited in a dose-dependent fashion by antifibronectin IgG and by GRGDSP, a synthetic peptide that mimics the amino acid sequence of the cell-binding domain of fibronectin. The authors conclude that a fibronectin/fibronectin receptor system mediates EGF-induced stimulation of cellular attachment. These findings suggest that EGF may increase the expression of fibronectin receptors.

Amino Acid Sequence↗
PubMed1992

Radiation-related ophthalmological changes and aging among Hiroshima and Nagasaki A-bomb survivors: a reanalysis.

The relationship of ionizing radiation to the age-related ophthalmological findings of the 1978-1980 ophthalmological examination of A-bomb survivors of Hiroshima and Nagasaki has been reanalyzed using DS86 eye organ dose estimates. The main purpose of this reevaluation was to determine whether age and radiation exposure, as measured using the recently revised dosimetry information (DS86), have an additive, synergistic, or antagonistic effect. The data in this study are limited to axial opacities and posterior subcapsular changes, for which a definite radiation-induced effect has been observed in Hiroshima and Nagasaki A-bomb survivors. The best model fitting for axial opacities gives a significant positive effect for both linear dose and linear age-related regression coefficients and a significant negative effect for an interaction between radiation dose and age. Such a negative interaction implies an antagonistic effect in that the relative risks in relation to radiation exposure doses become smaller with an increase in age. On the other hand, the best-fitting relationship for posterior subcapsular changes suggested a linear-quadratic dose and linear age-related effect. The estimate of the quadratic dose coefficient shows a highly negative correlation with age, but the negative quadratic dose term is extremely small and is of little biological significance.

Adult↗
PubMed1992

Scanning electron microscopy-energy dispersive spectroscopy and X-ray diffraction analyses of human salivary stones.

Ten salivary stones in the human submandibular gland were investigated by scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and X-ray diffraction analyses. The stones usually showed a lamellar pattern. SEM observations revealed cubical, plate-like, granular, small and large granules, polyhedral or globular structures in these stones. By X-ray powder diffraction analysis, the main constituents of salivary stones were found to be apatite and whitlockite. SEM-EDS analyses showed that Ca and P were the major elements, frequently accompanied by Mg and S, and less frequently by Na, Al, Si, Cl, K, Fe, Cu and Zn. Ca/P molar ratios ranged from 1.00 to 2.00 with the average of 1.53, showing two maxima of about 1.50 and 1.60. The Ca/P molar ratio of about 1.50 corresponded to the value of whitlockite. The Ca/P molar ratio of 1.60 corresponded approximately to the value of apatite.

Adolescent↗
PubMed1992

[Fluorescein fundus angiography of optic nerve head in primary open angle glaucoma and low tension glaucoma].

Fluorescein fundus angiography was performed at angle of 20 degrees in the 58 low tension glaucoma (LTG) eyes (30 cases) and 77 primary open angle glaucoma (POAG) eyes (41 cases) and the relation of the optic nerve head fluorescein changes to visual field disturbances (stage classification of Kosaki) was compared between POAG and LTG groups. The filling defect of fluorescein in the deep area and the decrease in number of superficial capillaries were observed in the optic nerve head. The filling defect area of fluorescein in the optic nerve head corresponding to Bjerrum scotoma was recognized even in the mild visual field disturbance cases of both LTG and POAG. The following findings were noted in both LTG and POAG cases; expansion of the filling defect area and the decrease in number of superficial capillaries in the same area with progression of visual field disturbances. Filling defect area of fluorescein of the optic nerve head accorded with visual field disturbance area in 19 LTG eyes (32.8%) and 61 POAG eyes (79.2%). On the contrary, the filling defect area of the optic nerve head was wider than the visual disturbance area in 37 LTG eyes (63.8%) and 16 POAG eyes (20.8%). These findings suggest that blood circulatory disorders of the optic nerve head occurred earlier in LTG than in POAG and that the development of LTG might be closely associated with the blood circulatory disorders.

Aged↗
PubMed1992

Increased lysosomal enzyme activity of keratocytes after endocytosis of foreign particles.

It has been reported that keratocytes endocytose foreign particles both in vitro and in vivo, suggesting the active participation of keratocytes in corneal wound healing and host defense mechanism. To understand the cellular response and the fate of engulfed foreign particles, we investigated the changes in the lysosomal enzyme activities after keratocytes endocytosed latex beads or glutaraldehyde-fixed Staphylococcus aureus. Acid phosphatase activity in the cells endocytosing either latex beads or fixed bacteria increased significantly as compared with that in the control over the period of 12 hours. Changes in acid phosphatase activity depended on both the incubation periods and the amount of latex beads or bacteria added. The activity reached a plateau after 6 hours of incubation. When keratocytes endocytosed latex beads, the activity of N-acetyl-beta-D-glucosaminidase in the cells showed an increase similar to that of acid phosphatase. However, the N-acetyl-glucosaminidase activity in the cells endocytosing fixed bacteria did not increase significantly. These findings suggest that endocytosing keratocytes increase degrading enzyme activities in the cells to break down engulfed foreign particles. It is also suggested that the intracellular response is varied according to the character of the engulfed materials.

Acetylglucosaminidase↗
PubMed1991

Hyaluronan stimulates corneal epithelial migration.

Hyaluronan (hyaluronic acid), well-known for its viscoelastic properties, is also recognized as a biological signal to cells. Using organ cultures of the rabbit cornea, we investigated the effects of hyaluronan on the migration of corneal epithelium. The addition of hyaluronan to the culture medium increased the length of the path of the corneal epithelial layer in a dose-dependent fashion. Other glycosaminoglycans (chondroitin, chondroitin sulphate, keratan sulphate and heparan sulphate) were also tried, but only hyaluronan exhibited a stimulatory effect on corneal epithelial migration. The effects of hyaluronan and fibronectin or epidermal growth factor (EGF) were additive; the addition of antisera against fibronectin or against EGF did not alter the stimulatory effect of hyaluronan. These results demonstrate that hyaluronan stimulates corneal epithelial migration by mechanism(s) different from those of fibronectin and EGF.

Animals↗
PubMed1991

H1 histone stimulates limited proteolysis of protein kinase C subspecies by calpain II.

Limited proteolysis of protein kinase C (PKC) subspecies with Ca2(+)-dependent neutral protease II (calpain II) was remarkably stimulated by basic polypeptides, such as H1 histone and poly-L-lysine. This stimulatory effect was observed for proteolysis of the active form of PKC, which was associated with phospholipid and diacylglycerol. The inactive form of PKC was far less susceptible to proteolysis, both in the presence and absence of the basic polypeptides. The basic polypeptides did not appear to interact with calpain II, but made the PKC molecule more susceptible to proteolysis. The relative rates of cleavage of type I (gamma), II (beta), and III (alpha) PKC were 2:2:1. The available evidence suggests that, like calpain I, calpain II may also contribute to the down-regulation or depletion of PKC.

Animals↗
PubMed1991

Morphological study of calcospherites in rat and rabbit incisor dentin.

Calcospherites from incisors of rats and rabbits were studied, by means of secondary and backscattered electron images, using scanning electron microscopy. Part of each incisor specimen was made anorganic to allow observation of the surface of the mineralization front by scanning electron microscopy; the other part was ground on one side for observation by scanning electron microscopy with a backscattered electron image detector. In both species the labial mineralization front was wavy and the image showed fused calcospherites, whereas the lingual mineralization front appeared to consist of a combination of linear and globular forms. In rat labial dentin the calcospherites were large and globular form, but they did not develop in the lingual dentin and were small and oval. The shape and size of rabbit incisor calcospherites varied from the pulp horn to the root apex. There were great differences between rats and rabbits with respect to the size and shape of the calcospherites at the mineralization front. This may be due to species differences and possibly the differing rates of dentinogenesis in rats and rabbits.

Animals↗
PubMed1991

Requirement of microtubule assembly for initiation of EGF-stimulated corneal epithelial migration.

To understand the mechanisms of epidermal growth factor (EGF)-stimulated re-epithelialization, the roles of microtubules and microfilaments in epithelial migration were investigated using the organ culture of rabbit cornea. The action of EGF was also compared with that of fibronectin. The addition of either EGF or fibronectin increased the epithelial sheet migration. Nocodazole, an inhibitor of the microtubule assembly, alone did not affect the epithelial migration. Nocodazole antagonized the EGF-dependent increase of the epithelial migration when nocodazole coexisted during the period of delivery of the signal from EGF. However, the stimulatory action of fibronectin was observed even in the presence of nocodazole. On the other hand, cytochalasin B, inhibitor of the microfilament assembly, inhibited the epithelial migration in a dose-dependent manner regardless of whether EGF or fibronectin was present or not. These results indicated that the formation of microfilaments was essential for the corneal epithelial migration and that the stimulatory action of EGF on the corneal epithelial migration depended on the assembly of microtubules. Therefore, in corneal epithelial wound healing, the action of EGF requires the organization of both microfilaments and microtubules, while that of fibronectin requires the reorganization of the microfilaments.

Actin Cytoskeleton↗
PubMed1991

[Assessment of the permeability of the pulmonary microvasculature using radiotracers in a case of adult respiratory distress syndrome].

A 48-year-old man with small cell lung cancer developed ARDS, and massive pulmonary edema fluid was obtained with the fiberoptic bronchoscopy. The pulmonary edema fluid to serum ratios of total protein and albumin were 0.72 and 0.85 respectively. The ratio of LDH was higher (2.71), while that of cholesterol was lower (0.11) than that of total protein. Simultaneously, isopropyl N [I-123] p iodoamphetamine (I-123 IMP) and I-131 human serum albumin (I-131 HSA) were injected into this patient. Samples of blood and pulmonary edema fluid were collected to measure the clearance through the pulmonary microvasculature. The time activity curves of I-123 IMP and I-131 HSA in his blood samples revealed almost constant radioactivity from 5 minutes to 120 minutes after injection, while both radioactivity levels in pulmonary edema fluid samples increased with time. The clearance ratio of I-123 IMP to I-131 HSA was constant at each sampling time (mean +/- SD, 1.51 +/- 0.32). The linear correlation between I-123 IMP clearance and I-131 HSA clearance (r = 0.95, p less than 0.01) suggested that the clearance ratio of exudative plasma components may remain unchanged even if pulmonary microvasculature permeability has changed.

Body Fluids↗