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Biomedical subjects

A Kanai

Publications and source records attributed to A Kanai.

At least 91 records · Page 5Linked to original sources
PubMed1996

Studies on the mechanism of early onset macular degeneration in cynomolgus (Macaca fascicularis) monkeys. I. Abnormal concentrations of two proteins in the retina.

Cynomolgus (Macaca fascicularis) monkeys from three families, which showed symptoms of early onset macular degeneration was studied. Two proteins, albumin and glyceraldehyde 3-phosphate dehydrogenase, were found to have markedly altered concentrations in whole retina of the monkeys with early onset macular degeneration, compared with normal controls. SDS-polyacrylamide gel patterns detected a 40-70% increase in the concentration of albumin and about 65% decrease in the concentration of glyceraldehyde 3-phosphate dehydrogenase in these affected retinas. There was however no significant difference in the relative concentrations of albumin in the plasma samples of affected and normal monkeys belonging to the three families studied and to an unrelated family. These initial findings suggest that degradative as well as antioxidant enzymes might be involved in the mechanisms leading to macular degeneration. In addition, the results also correlate with a possible role of these two proteins in H2O2 toxicity and appear to indicate that oxidative stress is significant in the etiology of early onset macular degeneration.

Albumins↗
PubMed1996

Studies on the mechanism of early onset macular degeneration in cynomolgus monkeys. II. Suppression of metallothionein synthesis in the retina in oxidative stress.

Initial investigations done in this laboratory detected increased albumin and decreased glyceraldehyde 3-phosphate dehydrogenase concentrations in the retina of an animal model manifesting early onset macular degeneration. Both glyceraldehyde 3-phosphate dehydrogenase and albumin are markers of oxidative stress in cells. In this study, we used the same animal model to study further biochemical and physiological processes which may be involved in the pathogenesis of early onset macular degeneration in monkeys. We detected 60% lower catalase and glutathione peroxidase activities in the affected retinas suggesting lower antioxidant activities and oxidative stress. One of the consequences of oxidative stress is the production of metallothionein, a low molecular weight protein also induced by high concentrations of heavy metals such as zinc. Metallothionein was detected by RT-PCR in these monkey retinas. However initial quantitative PCR studies on this protein showed that the synthesis of metallothionein in affected retinas appears to be less than in normal controls. The affected retinas also showed a fourfold lower zinc concentration compared with the normal controls. No significant difference, however, could be detected in the zinc concentrations in plasma samples. Since induction of metallothionein synthesis is mediated by transcription factors which require heavy metals such as zinc for binding to specific sites in the DNA, the lowered zinc concentration may, thus, correlate with the lowered metallothionein expression. And since metallothionein is suggested to function as a free radical scavenger, the lowered metallothionein synthesis may consequently contribute to increased peroxidation reactions in the affected retinas. It appears therefore, that oxidative stress and the decreased metallothionein synthesis may be involved in the pathogenesis of early onset macular degeneration in this animal model.

Amino Acid Sequence↗
PubMed1996

[Combination effect of vancomycin and cefpirome against methicillin-resistant Staphylococcus aureus in vitro--antimicrobial activities in postantibiotic phase].

The antimicrobial activities of vancomycin (VCM) or cefpirome (CPR) at sub- and above-MICs against clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) during the postantibiotic phase (PAE-phase) induced by CPR or VCM were examined. Antimicrobial activities were determined growth suppression (post antibiotic sub-MIC effect: PA SME) at sub-MICs, and bactericidal activity at sub- and above-MICs. During the PAE-phase induced by VCM, growth suppression and bactericidal activity of CPR were enhanced at sub-MICs, compared with the non PAE-phase. On the other hand, during the PAE-phase induced by CPR, not only were growth suppression and bactericidal activity of VCM enhanced at sub-MICs, but bactericidal activity were enhanced at above-MICs compared with non PAE-phase. These suggest that enhancement of growth suppression and bactericidal activity during PAE-phase was a factor of combination effect of VCM and CPR against MRSA.

Anti-Bacterial Agents↗
PubMed1996

[Six cases of secondary keratoconus with Fleischer's ring pattern corneal epithelial iron ring].

We observed 6 cases of secondary keratoconus with Fleischer's ring pattern corneal epithelial iron ring. These 6 cases were 2 males and 4 females. The causes of secondary keratoconus were 2 cases of trachoma, 2 cases of trauma, 1 case of keratitis, and 1 case of unknown origin. All showed thinning of the cornea and Fleischer's ring pattern corneal epithelial iron ring. After penetrating keratoplasty of 1 case, the button of the recipient showed the deposition of hemosiderin in the corneal epithelium stained blue by Prussian blue. At the same time we confirmed the existence of iron in the corneal epithelium by the X-ray ultimate analysis. Fleischer's ring is considered to be characteristic of keratoconus, but we have found that Fleischer's ring is also seen in secondary keratoconus in which the cornea becomes thinner secondarily for some reason.

Adult↗
PubMed1996

[Glycosaminoglycans in subepithelial opacity after excimer laser keratectomy].

We evaluated histochemically the characteristics of glycosaminoglycans and proteoglycans in the corneal subepithelial opacity after excimer laser keratectomy on rabbit corneas. We also performed the same evaluations on the cornea after mechanical keratectomy. Twenty days after the operations, the area immediately subjacent to the epithelium showed strong staining with toluidine blue, alcian blue, and colloidal iron. However, after treatment with chondroitinase ABC or chondroitinase AC, alcian blue staining in this area decreased dramatically. Antilarge proteoglycan antibody also reacted strongly in this area. Histochemical and immunohistochemical examination of the cornea where mechanical keratectomy was done showed basically similar findings with the cornea of excimer laser keratectomy. These results suggest that large-molecula proteoglycans with chondroitine sulfate side chains become localized in the subepithelial area after two different kinds of keratectomies. We presume from histochemical and immunohistochemical observations that the subepithelial opacity observed after excimer laser keratectomy is not a special reaction to excimer laser but simply a corneal scar formed after stromal resection.

Animals↗
PubMed1996

Non-contact specular microscopic observation for early response of corneal endothelium after contact lens wear.

PURPOSE: Contact lenses induce short- and long-term corneal endothelial changes, including endothelial blebs. The endothelial bleb is a reversible, short-term response found on the corneal endothelium after lens wear. We used non-contact specular microscopy to observe endothelial blebs occurring with different types of contact lenses. METHODS: We observed the time course, frequency, and location of endothelial blebs in 11 eyes of 9 contact lens wearing patients. Eight types of contact lenses with various oxygen transmissibilities (Dk/L) were used in the study. RESULTS: Blebs were observed in the central cornea in patients with polymethylmethacrylate and rigid gas permeable contact lenses, while blebs in the central to mid-peripheral cornea were seen in patients wearing soft contact lenses. CONCLUSIONS: Although the number of blebs vary by individual patient, there appears to be an inverse correlation between the number of blebs and the Dk/L of the contact lens.

Adult↗
PubMed1996

Cloning and high expression of rabbit FKBP25 in cornea.

Rabbit 25 kDa FK-506/rapamycin binding protein (FKBP25) cDNA was isolated during a screening of rabbit corneal endothelial cDNA library. The cDNA clone was a 955 bp fragment with a 670 bp open reading frame and a 285 bp 3' non-coding region. The cDNA and deduced amino acid sequences were 91.7 and 96.4% identical, respectively, to previously reported human FKBP25B sequences. The lysine-rich region KK(X)7KK(X)26KKKK, which plays an important role in nuclear translocation in rabbit FKBP25, was recognized. Reverse transcription-polymerase chain reaction (RT-PCR) amplification of rabbit FKBP25 and FKBP12 in selected rabbit organs, including total cornea, showed higher expressions in cornea, retina, cerebrum and cerebellum than other compared tissues. RT-PCR amplification in rabbit cultured corneal cells showed expressions in all cultured corneal epithelial, stromal, endothelial, and especially in SV40-adenovirus vector-immortalized epithelial cells. The higher expressions of FKBP25 and FKBP12 suggest significant roles for FKBPs in those tissues.

Amino Acid Sequence↗
PubMed1995

Poly(U) binding activity of hepatitis C virus NS3 protein, a putative RNA helicase.

A non-structural protein of the hepatitis C virus (HCV), NS3, contains amino acid sequence motifs characteristic of serine-proteinases and RNA helicases. RNA binding activity of the NS3 protein with an apparent dissociation constant of 2 x 10(-7) M was detected using a poly(U)-Sepharose resin. Competitive RNA binding analysis suggested that the NS3 protein binds preferentially to the poly(U) sequence, which is located at the 3' end of HCV RNA. Mutational analysis of NS3 protein revealed the possibility that both the RNA helicase region and the serine-proteinase region were necessary for full RNA binding activity.

Amino Acid Sequence↗
PubMed1995

Missense mutation of rhodopsin gene codon 15 found in Japanese autosomal dominant retinitis pigmentosa.

Heterozygous missense mutation in codon 15 of the rhodopsin gene was detected in a patient with autosomal dominant retinitis pigmentosa (ADRP), where a transition of adenine to guanine at the second nucleotide in codon 15 (AAT-->AGT), corresponding to a substitution of serine residue for asparagine residue (Asn-15-Ser) was detected. None of the remaining unrelated 42 ADRP, 24 autosomal recessive RP (ARRP) and 34 normal individuals had this alteration. Her funduscopic findings were sectorial in type similar to that of the patients with the same mutation found in an Australian pedigree (Sullivan et al., 1993). This study shows phenotypic similarities in patients with the same mutation of a different ancestry.

Amino Acid Sequence↗
PubMed1995

Clinical and histopathologic features of corneal dystrophies in Japan.

PURPOSE: To examine retrospectively the frequency of various corneal dystrophies among Japanese patients who underwent keratoplasty or keratectomy at the authors' institution over a 34-year period, and to compare the histopathologic features of these disorders in the Japanese population with those reported in the Western literature. METHODS: Corneal specimens obtained during keratectomy or keratoplasty (lamellar and penetrating) performed at the authors' institution from 1959 through 1992 were reviewed. Immunohistochemical studies were performed using monoclonal antibodies to keratan sulfate and gelsolin, as well as two lectins (concanavalin A and wheat germ agglutinin). RESULTS: Of 1259 corneal specimens, 159 (12.6%) specimens from a total of 80 patients showed corneal dystrophy. Virtually all were non-Fuchs dystrophies; only one case of primary Fuchs dystrophy was identified histologically. Granular dystrophy and gelatinous drop-like dystrophy were the most common dystrophies identified in the specimens, largely because of multiple specimens from individual patients with recurrent disease. These two disorders accounted for 86 of the 159 specimens. In terms of numbers of patients, lattice dystrophy was the most common (26 patients, 32.5%), followed by macular dystrophy (16 patients, 20%), gelatinous drop-like dystrophy (15 patients, 18.8%), granular dystrophy (14 patients, 17.5%), and Avellino dystrophy (3 patients, 3.75%). Dystrophies represented by only one or two patients included congenital hereditary endothelial dystrophy, primary spheroidal keratopathy, posterior polymorphous dystrophy, Schnyder crystalline dystrophy, and Fuchs dystrophy. CONCLUSIONS: This histopathologic study showed a very low incidence of Fuchs dystrophy in the authors' Japanese patient population, compared with the incidences seen in studies of populations in Western countries. Of the non-Fuchs dystrophies, lattice dystrophy was the most common among the patients, although there were large numbers of specimens with granular dystrophy and gelatinous drop-like dystrophy due to their recurrent character. The causes of clinical and histopathologic differences and similarities among the Japanese patients and the patients described in the Western literature are likely related to genetic factors, but a complete understanding of their specific mechanisms awaits future molecular biologic and genetic elucidation.

Antibodies, Monoclonal↗
PubMed1995

Expression of recombinant human thyrotropin receptor in myeloma cells.

Starting with a previously isolated cDNA for human thyrotropin receptor (TSHR), we established a transformed myeloma cell line, SP56, which expresses human TSHR on its cell surface. Binding analysis showed that SP56 bears 1.1 x 10(5) TSHR per cell with a Kd of 2.2 x 10(-10) M. Using the purified cellular membrane, we established a TSH binding inhibition immunoglobulin (TBII) assay for autoantibodies against TSHR. We compared it with the TBII assay utilizing porcine thyroid membranes expressing porcine TSHR, which has been widely used for TBII assay, by using 96 serum samples from patients with autoimmune thyroid disease and normal individuals. Our TBII assay was more sensitive than the one using porcine TSHR: of 38 sera of patients which were judged negative for autoantibodies to TSHR (TBII value below 10%) by the latter assay, 28 were positive (above 20%) in our assay. By using a perfusion culture system, we obtained as many as 3 x 10(10) SP56 cells, from which 3,450 mg protein of the membrane could be purified; this is sufficient for 15,000 assays. The results indicate that the membrane of the myeloma cell line SP56 is more suitable for use in the TBII assay than the porcine thyroid membrane, in terms of sensitivity to autoantibodies against TSHR in human sera.

Animals↗
PubMed1995

Optical mapping reveals that repolarization spreads anisotropically and is guided by fiber orientation in guinea pig hearts.

Guinea pig hearts were stained with a voltage-sensitive dye and imaged on a photodiode array to record fluorescent action potentials (APs) from 124 sites. Activation and repolarization patterns were recorded from the epicardium during stimulation at different loci and correlated with the underlying fiber architecture. Endocardial APs were recorded by inserting a light guide into the ventricular cavity or by dissecting out the ventricular free wall to expose the endocardium. In hearts paced on the right atrium to simulate sinus rhythm, activation emerged synchronously over a large area of the ventricular epicardium and spread laterally in 5 to 7 ms. The apparent longitudinal and transverse velocities were 2.66 +/- 0.11 and 1.65 +/- 0.09 m/s (n = 12). In contrast, repolarization began near the apex on the endocardium and spread transmurally in 6 +/- 1.3 ms (n = 12) and then anisotropically along the epicardium in 25 to 30 ms with apparent maximum (0.53 +/- 0.11 m/s) and minimum (0.31 +/- 0.10 m/s) repolarization velocities that aligned with the longitudinal and transverse axes of epicardial fibers. When paced on the epicardium, activation of intact hearts (n = 12) and perfused sheets (n = 8) was anisotropic, with longitudinal (0.85 +/- 0.05 m/s) and transverse (0.44 +/- 0.04 m/s) conduction velocities that aligned with the epicardial fiber orientation. When activation was initiated at different sites on the epicardium, repolarization always began near the apex and exhibited patterns similar to those obtained under right atrial pacing, but with slower longitudinal (0.41 +/- 0.09 m/s) and transverse (0.23 +/- 0.07 m/s) repolarization velocities (n = 18). In sheets stretched parallel to the longitudinal axis of surface fibers, AP durations (APDs) increased as a function of fiber length, from the length at zero developed tension to 120% of the length at maximum developed tension (Lmax). Spatial distributions of APDs did not change during stretches along the rising phase of the length-tension curve. In sheets stretched to 50% of Lmax, APDs were shorter and more homogeneous on the endocardium (mean APD, 188 ms; delta APD, 195-186 = 9 ms) than on the epicardium (mean APD, 204 ms; delta APD, 212-186 = 26 ms; n = 8). In guinea pig hearts, activation is rapid; therefore, repolarization depends primarily on intrinsic spatial heterogeneities of APDs. Consequently, repolarization begins at endocardial cells with the shortest APDs and spreads transmurally and then anisotropically on the surface according to the epicardial cell orientation.

Animals↗
PubMed1995

Clinical features of Japanese Leber's hereditary optic neuropathy with 11778 mutation of mitochondrial DNA.

The G to A transition of nucleotide position (nt) 11778 of mitochondrial DNA (mtDNA) has been frequently observed in Japanese Leber's hereditary optic neuropathy (LHON) cases. Therefore, we performed a multi-institutional study in Japan of LHON cases with this 11778 mutation of the mtDNA. Genetic and clinical data on 108 cases (90 affected and 18 carriers) in 79 unrelated families were obtained from 64 Japanese institutions. Detection of the nt11778 mutation was performed using restriction enzymes (74 cases) or dot blot with allele specific oligonucleotide (34 cases). Heteroplasmy was observed in 13 of the 90 affected cases and in 8 of the 18 carrier cases. Forty-five families had family history of LHON (44 maternal inheritance, 1 undetermined), and in 28 families (35.9%) there were isolated cases. The male-to-female ratio in the affected was 82:7 (92.1% male). The age at onset of visual loss ranged from 7 to 59 years (average: 23.4 years). All cases had bilateral involvement except one case with a blind eye resulting from ocular infection during childhood. Onset interval between the two eyes ranged from simultaneous to 17 months (average: 2.5 months), in 91.3% of cases being under 6 months. Visual acuity was 0.1 or worse in 152 (85.9%) of 177 eyes, only 6 eyes showing over 0.5. Progression of visual loss ranged from 0 to 48 months (average: 6.2 months). Central visual field abnormality was observed in 162 eyes (96.4%) of 168 eyes. Nonsuspect fundus in the ophthalmoscopic examination constituted 22.8% of eyes. Systemic corticosteroid was given to 45 (52.9%) of 85 cases and visual acuity was improved in only 2 cases (4.4%). Arrhythmia, neurological and muscular abnormality were observed as rare general complications. The present survey indicates that the male-to-female ratio is higher than the previous Japanese LHON statistics and that the visual outcome is better than in American LHON cases with the 11778 mutation.

Adolescent↗
PubMed1995

[Correlation between corneal sensitivity and nerve regeneration following excimer laser ablation].

To compare the recovery of corneal sensitivity and corneal regeneration following excimer laser and manual epithelial debridement, the corneal epithelium of the right eye of New Zealand white rabbits (n = 21) was manually debrided and the left eye was ablated with the excimer laser (47 microns depth, 5 Hz, and 160 mJ/cm2). We observed the wound healing rate and corneal sensitivity. The relative density of innervation on the intraepithelial layer was measured using gold chloride staining or right microscopic examination for 30 weeks. In the laser-ablated cornea sensitivity rapidly increased to a normal level by day 5, and then it continued to increase gradually and reached a maximum at day 42. Thereafter it remained elevated to 126 days and returned to normal at 210 days. There were significant differences in the recovery of sensitivity following excimer ablation and manual epithelial removal. The relative density of innervation on the intraepithelial layer after excimer ablation was significantly higher than manual debridement at day 35. We observed a correlation between increased sensitivity levels and increased nerve density. This result suggests that for photorefractive keratectomy or phototherapeutic keratectomy, manual debridement of the corneal epithelium should be performed before stromal excimer ablation.

Animals↗
PubMed1995

[Incidence of tumors and tumor-like lesions in the conjunctiva and the cornea].

Incidence of tumors and tumor-like lesions in conjunctiva and cornea seen at Juntendo University during the 13-year period from 1980 to 1992 was analysed histopathologically. There were 126 cases including 116 benign (92.1%) and 10 malignant lesions (7.9%). Pigmented nevi (32 cases) were most frequently found, accounting for 27.6% of the benign tumors and tumor-like lesions, half of which were compound nevi (16 cases). Nevi were closely followed by cysts (24 cases, 20.7%) and dermoids (15 cases, 12.9%). Carcinoma in situ (3 cases) was most frequently found, accounting for 30% of the malignant tumors (10 cases), closely followed by malignant lymphoma (2 cases), squamous cell carcinoma (2 cases), mucinous carcinoma (1 case), sebaceous gland carcinoma (1 case) and metastatic tumor (1 case). The ratio of males to females was 4:6. Age distribution of the patients was 47-92 years.

Adolescent↗
PubMed1995

[Clinical importance of inclusion cysts of nevi in bulbar conjunctiva].

We investigated 30 cases of nevi in bulbar conjunctiva histopathologically from 1980 to 1992. The patients' ages were between 5 and 85 years old (mean, 21 years). Investigated parameters of the tumors were the location, growth pattern, and the presence of inclusion cysts, melanin granules, goblet cells, and feeding vessels. Of 30 cases, 26 cases (87%) had inclusion cysts which were characteristic findings of conjunctival nevi. The mucous secretion from goblet cells may play an important role in the synthesis of inclusion cysts, but goblet cells were not found in 9 cases. This finding suggests that other secretory cells may be present. Four cases without inclusion cysts consisted of flat tumors. From this finding, the presence of inclusion cysts may be related to the growth of tumors. We conclude that the growth of the pigmented conjunctival tumors with inclusion cysts suggests a benign growth pattern. A periodical follow-up study or biopsy should be performed, if inclusion cysts are not found.

Adolescent↗
PubMed1995

Development of a new soft gas permeable contact lens with Dk 300.

The effects on the rabbit cornea of a new gas permeable nonhydrophilic soft contact lens made of newly designed polymer with a Dk value of 300 were studied physiologically, histologically, and histochemically during 5 days of daily wear followed by 14 days of extended wear. Corneal swelling was observed to be within 10% of corneal thickness during the wear period. No serious corneal surface changes were observed. Specular microscopy showed no endothelial changes in terms of cell density, coefficient of variation of cell area (CV), or hexagonality before and 2 weeks after lens wear. Histochemical study using periodic acid-Schiff staining and histological study with hematoxylin-eosin revealed no remarkable changes. Scanning electron microscopy revealed slight focal changes; there were no significant changes. The results show that the new soft gas permeable contact lens has no harmful effect on the rabbit cornea.

Animals↗