Biomedical subjects

N Yokoi

Publications and source records attributed to N Yokoi.

At least 19 recordsLinked to original sources

PubMed2004

Functional aspects of the tear film lipid layer.

The lipid layer is an essential component of the tear film, providing a smooth optical surface for the cornea and retarding evaporation from the eye. The meibomian lipids which compose it are well adapted for this purpose. They form a thin, smooth film whose thickness, and probably composition, influences the rate of evaporation. Their melting range ensures sufficient fluidity for delivery to the tear film from the lid margin reservoirs, while the film itself may exhibit a higher viscosity at the cooler temperature of the ocular surface. The factors governing lipid film formation during the blink are not fully understood, but one view is that the polar lipids, interacting with the aqueous sub-phase of the tear film, spread in advance of the non-polar components, which form the bulk of the film. The meibomian lipids stabilise the tear film by lowering its free energy; they carry water into the film during its formation and interact with lipid-binding proteins in the aqueous phase, such as tear lipocalin. The lipocalins, complexed with other tear components, may also contribute to the high, non-Newtonian viscosity of the tear film and its low surface tension, features which are essential for tear film stability. Formation of the lipid film is a complex process. Lipid is delivered to the tear film in the up-phase of the blink, more from the lower than the upper reservoir. The lipid layer comes to a stop well after completion of the blink and remains relatively immobile until it is compressed in the down-phase of the blink that follows. Then, it either retains its structure in a series of subsequent blinks, or is completely re-constituted after mixing with the reservoir lipids. Delivery of meibomian lipid to the marginal reservoirs is mainly the result of continuous secretion, under neural and hormonal control, supplemented by lid action. The reservoirs provide a hydrophobic barrier to tear overspill and to contamination by skin lipids which might destabilise the tear film. They probably also provide the chief route for meibomian lipid excretion.

Adolescent↗

PubMed2004

Polymorphic variation in the CBLB gene in human type 1 diabetes.

CBLB was evaluated as a candidate gene for type 1 diabetes (T1D) susceptibility based on its association with autoimmunity in animal models and its role in T-cell costimulatory signaling. Cblb is one of the two major diabetes predisposing loci in the Komeda diabetes-prone (KDP) rat. Cbl-b, a ubiquitin ligase, couples TCR-mediated stimulation with the requirement for CD28 costimulation, regulating T-cell activation. To identify variants with possible effects on gene function as well as haplotype tagging polymorphisms, the human CBLB coding region was sequenced in 16 individuals with T1D: no variants predicted to change the amino-acid sequence were identified. Seven single-nucleotide polymorphism (SNP) markers spanning the CBLB gene were genotyped in multiplex T1D families and assessed for disease association by transmission disequilibrium testing. No significant evidence of association was obtained for either individual markers or marker haplotypes.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Ophthalmic artery blood flow in patients with internal carotid artery occlusion.

AIM: To evaluate the risk factors for rubeosis iridis by colour Doppler imaging (CDI) in patients with complete internal carotid artery occlusion (ICAO). METHODS: 34 eyes of 32 consecutive patients with complete ICAO were enrolled. Using CDI, blood flow direction (forward, reverse, undetectable) in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary artery (SPCA) were determined. Arterial mean blood velocity (Vmean) and resistive index (RI) were calculated and correlations between the rubeosis iridis incidence and CDI parameters analysed. RESULTS: The eyes were classified into four types according to blood flow direction: forward flow in OA, CRA, and SPCA (type 1; n = 11); reverse OA and forward CRA and SPCA flow (type 2a; n = 12); reverse OA and undetectable CRA and SPCA flow (type 2b; n = 8); undetectable flow in all three arteries (type 3; n = 3). Rubeosis iridis was seen only in type 2b and 3 eyes. Type 2b showed significantly (p<0.01) higher Vmean and lower RI values in the OA, indicating more rapid reverse flow than in type 2a eyes. Although in type 1 and 2a eyes OA flow was in opposite directions, they manifested no rubeosis iridis and no difference in the Vmean and RI values of the CRA and SPCA. CONCLUSIONS: The classification of eyes from patients with ICAO into four types by CDI may facilitate the identification of the eyes at high risk for rubeosis iridis. Markedly diminished flow in both the CRA and SPCA may result in rubeosis iridis, regardless of OA flow direction.

Adult↗

PubMed2001

Characterization of the gene EPAC2: structure, chromosomal localization, tissue expression, and identification of the liver-specific isoform.

The liver-specific protein cAMP-GEFII (also known as Epac2) belongs to a family of cyclic adenosine monophosphate (cAMP) binding proteins having guanine nucleotide exchange factor (GEF) activity (the cAMP-GEF family). Here we clone the gene EPAC2, encoding cAMP-GEFII, from a human liver cDNA library. Human EPAC2 has at least 31 exons and is mapped to human chromosome 2q31. Analyses by primer extension, reverse transcriptase-polymerase chain reaction, and in situ hybridization revealed the presence of three transcription start sites of liver-specific Epac2: two major sites located in exon 10 and a minor site in intron 9. The same translation start site is used in all three transcripts. Liver-specific cAMP-GEFII protein, which lacks the first cAMP-binding domain and the Dishevelled/Egl-10/Pleckstrin domain, was detected at 79 kDa by immunoblot analysis, confirming the presence of the short form of cAMP-GEFII in the liver. Liver-specific cAMP-GEFII also has GEF activity toward Rap1. These results demonstrate the presence of liver-specific cAMP-GEFII. Together with the previous finding that cAMP-GEFII is responsible for cAMP-dependent exocytosis in secretory cells, our study suggests that cAMP-GEFII may have a distinct role in liver.

Amino Acid Sequence↗

PubMed2001

A longitudinal study of disturbances of the hypothalamic-pituitary-adrenal axis in women with progestin-negative functional hypothalamic amenorrhea.

OBJECTIVE: To longitudinally evaluate disturbances of the hypothalamic-pituitary-adrenal (HPA) axis in women with secondary progestin-negative hypothalamic amenorrhea. DESIGN: Retrospective cohort study. SETTING: Yokohama City University, Yokohama, Japan. PATIENT(S): Twenty-four women with progestin-negative hypothalamic amenorrhea. INTERVENTION(S): Administration of human corticotropin-releasing hormone (hCRH) and treatment with a combination of estrogen and progesterone. MAIN OUTCOME MEASURE(S): Plasma cortisol and ACTH concentrations and period required for recovery from amenorrhea. RESULT(S): Plasma ACTH concentrations 30 and 60 minutes after injection of hCRH and the percent maximum increment (%Cmax) of ACTH were significantly lower in the amenorrheic patients compared with the control group patients. The basal cortisol was significantly higher, and the %Cmax of cortisol was significantly lower. In the 16 patients who recovered from amenorrhea, there was a significant positive correlation (Y = 1.93X-10.8, r = 0.629) between the basal cortisol concentrations (X) and the period for recovery (Y). The serum E2 gradually increased before recovery, and this E2 increase was preceded by changes in the plasma cortisol concentration and the %Cmax values of cortisol and ACTH. CONCLUSION(S): The CRH test might be useful for evaluating the roles of stress and for estimating the period required for recovery in hypothalamic amenorrhea.

Adrenocorticotropic Hormone↗

PubMed2001

Investigation of Corneal Autofluorescence in Diabetic Patients.

Purpose: The investigation of corneal autofluorescence in diabetic patients.Objects and Methods: Corneal autofluorescence was investigated with a newly-developed fluorophotometer (wave length: excitation, 290-390 nm; emission, 430-630 nm) having, fluorescence characteristics involving those of reduced pyridine nucleotides (PN) and advanced glycation endoproduct (AGE) except pentosidine and pyrraline. Twenty-eight patients with non-insulin-dependent diabetes mellitus and sixty-seven healthy volunteers were studied.Results: The corneal autofluorescence was 1.65 times higher than that of controls (P <.0001). In non-insulin-dependent diabetes mellitus, the corneal autofluorescenece was not correlated significantly with various diabetic parameters in blood (r < 0.4). In controls, the corneal autofluorescence was correlated significantly with age (r = 0.438).Conclusion: The corneal autofluorescence has some relation with PN and AGE accumulation in the cornea.

Journal Article↗

PubMed2001

Characteristics of the human ocular surface epithelium.

An appreciation of the biological characteristics of the human ocular surface epithelium affords us a great insight into the physiology of the human ocular surface in health and disease. Here, we review five important aspects of the human ocular surface epithelium. First, we recognize the discovery of corneal epithelial stem cells, and note how the palisades of Vogt have been suggested as a clinical marker of their presence. Second, we introduce the concept of the gene expression profile of the ocular surface epithelium as arrived at using a new strategy for the systematic analysis of active genes. We also provide a summary of several genes abundantly or uniquely expressed in the human corneal epithelium, namely clusterin, keratin 3, keratin 12, aldehyde dehydrogenase 3 (ALDH3), troponin-I fast-twitch isoform, ssig-h3, cathepsin L2 (cathepsin V), uroplakin Ib, and Ca(2+)-activated chloride channel. Genes related to limbal and conjunctival epithelia are also described. Third, we touch upon the genetic abnormalities thought to be involved with epithelial dysfunction in Meesmann's dystrophy, gelatinous drop-like corneal dystrophy, and the ssig-h3-mutated corneal dystrophies. Fourth, we provide an update regarding the current state of knowledge of the role of cytokines, growth factors and apoptosis in relation to ocular surface homeostasis and tissue reconstruction; the main factors being epidermal growth factor (EGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), transforming growth factor-ss (TGF-ss), and some inflammatory cytokines. Fifth, corneal epithelial barrier function and dysfunction as measured by fluorophotometry is remarked upon, with an explanation of the FL-500 fluorophotometer and its ability to detect corneal epithelial dysfunction at a subclinical level. The research described in this review has undoubtedly generated a complete understanding of corneal epithelial pathophysiology-an understanding that, directly or indirectly, has helped advance the development of new therapeutic modalities for ocular surface reconstruction.

Apoptosis↗

PubMed2001

The detection of bacteria and bacterial biofilms in punctal plug holes.

PURPOSE: An investigation into bacterial biofilm formation on and in punctal plugs. METHODS: The study involved 21 patients with severe dry eye whose puncta were occluded by the use of punctal plugs. Of these, 15 had Sjögren's syndrome, 3 had non-Sjögren's syndrome, 2 had Stevens-Johnson syndrome, and 1 had graft-versus-host disease. From 17 of the 21 subjects, 18 samples of material were extracted from the holes of the punctal plugs (16 unilateral and 1 bilateral) and were subjected to enrichment culture. Nineteen punctal plugs were removed and processed for electron microscopy: 15 by scanning electron microscopy, and 4 by transmission electron microscopy. RESULTS: Positive cultures were found in 8 of 18 (44%) samples of the material extracted from the holes of punctal plugs. In six of these eight cases (75%) the cultured bacterial species was Staphylococcus epidermidis, whereas in the other two cases (25%) it was S. aureus. In 8 of the 15 punctal plugs examined by scanning electron microscopy and in the material extracted from 1 plug that was examined by transmission electron microscopy, there was clear evidence of bacterial colonization. CONCLUSION: Careful observation of patients with punctal plugs is important. If material accumulates in or on a punctal plug, it may contain bacteria and may form a bacterial biofilm. In these cases, replacement of the plug, clearing of the hole, or an alternative treatment should be considered.

Adult↗

PubMed2001

Unique occurrence of the 1CF11 carbohydrate epitope in primate saliva.

We examined a large number of individual human and animal saliva samples for the reactivity with ICF11, a mouse monoclonal antibody previously produced for the characterization of human milk mucin and apparently recognizing a certain carbohydrate antigenic structure shared by various human glycoproteins in secretions. The results obtained here confirm the unique occurrence of ICF11 epitope in each and every saliva sample from humans and Old world monkeys as well, though a vast variety was observed among individual saliva samples in the immunological reactivity with ICF11.

Animals↗

PubMed2001

Linkage mapping of the mouse nephrosis (nep) gene to chromosome 15.

ICGN is a partially inbred strain of mice with nephrotic syndrome caused by spontaneous glomerular lesion. It has been reported that the albuminuria in ICGN mouse was controlled by at least a single autosomal recessive gene (nep). In this study, we mapped the nep locus by linkage analysis of backcross progeny between ICGN and MSM mice using DNA pooling method. The linkage analysis revealed that the nep locus was localized on the distal part of chromosome 15.

Animals↗

PubMed2001

The Pro12 -->Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes.

The allele frequencies for a Pro12-->Ala substitution in peroxisome proliferator-activated receptor-gamma differ among ethnic groups, and its relationship with diabetes and associated diseases is controversial. The prevalence of this polymorphism and its effects on clinical characteristics have now been evaluated with a large number of Japanese individuals with type 2 diabetes (n = 2,201) and normal control subjects (n = 1,212) recruited by 10 institutions located in seven different cities in Japan. The allele frequency for the Ala12 variant was significantly lower in the type 2 diabetic group than in the control group (2.39 vs. 4.13%, P = 0.000054). However, compared with subjects without the Ala12 variant, the diabetic subjects with this variant exhibited a significantly higher serum concentration of total cholesterol (P = 0.001), manifested a reduced capacity for insulin secretion as evaluated by homeostasis model assessment (P = 0.007), and tended to possess a higher level of HbA1c. These data suggest that the Ala12 variant is associated with a reduced risk for the development of diabetes in the general population, but that it may be also a risk factor for insulin deficiency and disease severity in individuals with type 2 diabetes.

Adult↗

PubMed2001

[Adverse effects of beta-blocker eye drops on the ocular surface].

PURPOSE: We investigated the adverse effects of beta-blocker eye drops on tears and ocular surface epithelium. METHODS: We studied twenty-three eyes of twenty three glaucoma patients [10 males, 13 females: 53.8 +/- 12.2 (yrs; mean +/- standard deviation)] treated with beta-blocker eye drops for more than three months and thirty two control subjects (16 males, 16 females: 50.4 +/- 10.9). The parameters described below were compared between the groups: 1. the radius of tear meniscus curvature, 2. grades for tear lipid layer interference patterns, 3. non-invasive breakup time (N-BUT), 4. cotton thread value, 5. scores of fluorescein staining, 6. fluorescein breakup time (F-BUT), 7. scores of rose bengal staining, 8. and Schirmer I value. RESULTS: The glaucoma group showed a significant decrease in the radius of tear meniscus curvature (p = 0.0007), a significantly lower distribution in the grades for tear lipid layer interference patterns (p = 0.0270), a significant difference in the scores of fluorescein staining (p < 0.0001), a significant shortening in F-BUT (p = 0.0050), a significantly higher distribution in the scores of rose Bengal staining (p = 0.0010), and a significantly smaller value in Schirmer I value (p = 0.0042). However, there was no significant difference in N-BUT and cotton thread value. CONCLUSIONS: These results clearly demonstrate that the ocular surface in glaucoma patients treated with beta-blocker eye drops show dry-eye-like changes in terms of tears and ocular surface epithelium.

Adrenergic beta-Antagonists↗

PubMed2001

[Effect of latanoprost on the barrier function of corneal epithelium].

PURPOSE: We evaluated the effect on corneal epithelium barrier function of instillation of prostaglandin F2 alpha ophthalmic solution (latanoprost) for one month. MATERIALS AND METHODS: Ten healthy volunteers and nine glaucoma patients were enrolled in this study. The barrier function was determined as uptake of topically applied sodium fluorescein by the central cornea measured with an anterior fluorophotometer(FL-500, Kowa Co. Ltd). Healthy volunteers and glaucoma patients received 0.005% latanoprost instillation once daily for one month. We measured the uptake of fluorescein by the cornea of each subject before and one month after instillation. RESULTS: Fluorescein uptake before the instillation was 22.2 +/- 16.0 ng/ml (mean +/- standard deviation) and 26.4 +/- 15.1 ng/ml one month after the treatment in the normal group, and it was 55.0 +/- 25.0 ng/ml before treatment and 57.8 +/- 37.0 ng/ml after treatment in the glaucoma group. There was no significant difference in the uptake of fluorescein before and after treatment in either of two groups. CONCLUSION: These results suggested that the barrier function of corneal epithelium was not compromised after the instillation of latanoprost for at least one month.

Adult↗

PubMed2000

A novel low-density lipoprotein receptor-related protein mediating cellular uptake of apolipoprotein E-enriched beta-VLDL in vitro.

We report here the identification of a novel member of the low-density lipoprotein receptor (the LDL receptor) family through signal sequence trap screening of a mouse lymphocyte cDNA library. The protein was termed LDL receptor-related protein 9 (LRP9). LRP9 is a type I membrane protein predicted to contain 696 amino acids with a calculated molecular mass of 74 764 Da. The NH(2)-terminal half of LRP9 contains two CUB domains separated by a single ligand-binding repeat. The second CUB domain is followed by a cluster of three additional ligand-binding repeats and a transmembrane domain. The COOH-terminal intracellular region contains a proline-rich region. LRP9 mRNA was expressed in the liver, kidney, lung, and heart at high levels, and in the spleen and brain at low levels. In situ hybridization analysis of mouse liver, kidney, and brain detected LRP9 transcripts in hepatocytes, sinusoidal lining cells, peritubular capillaries, choroid plexus, ependyma of the third ventricle, pia matter, and hippocampus. In particular, high levels of expression were observed in the vascular walls. Apolipoprotein E (apoE)-enriched beta-VLDL stimulated cellular cholesteryl ester formation in ldl-A7/LRP9. These results raise the possibility that this newly identified receptor, which is expressed in the liver, may play a physiological role in the uptake of apoE-containing lipoproteins.

Adult↗

PubMed2000

MTABC3, a novel mitochondrial ATP-binding cassette protein involved in iron homeostasis.

Atm1p, a mitochondrial half-type ATP-binding cassette (ABC) protein in Saccharomyces cerevisiae, transports a precursor of the iron-sulfur (Fe/S) cluster from mitochondria to the cytosol. We have identified a novel half-type human ABC protein, designating it MTABC3 (mammalian mitochondrial ABC protein 3). MTABC3 mRNA is ubiquitously expressed in all of the rat and human tissues examined. MTABC3 protein is shown to be present in the mitochondria, as assessed by immunoblot analysis and confocal microscopic analysis of subcellular fractions of Chinese hamster ovary cells stably expressing MTABC3. Accumulation of iron in the mitochondria, mitochondrial DNA damage, and respiratory dysfunction in the yeast ATM1 mutant strain (atm1-1 mutant cells) were almost fully reversed by expressing MTABC3 in these mutant cells. These results indicate that MTABC3 is a novel ortholog of the yeast and suggest an important role in mitochondrial function. Interestingly, the human MTABC3 gene has been mapped to chromosome 2q36, a region within the candidate locus for lethal neonatal metabolic syndrome, a disorder of the mitochondrial function associated with iron metabolism, indicating that MTABC3 is a candidate gene for this disorder.

ATP-Binding Cassette Transporters↗

PubMed2000

Genetic mapping of the rat mutation creeping and evaluation of its positional candidate gene reelin.

We have previously described a rat autosomal recessive mutation, creeping (cre), causing severe ataxia and disarrangement of neuronal cells in the central nervous system. The mutant strain has recently been successfully inbred, named Komeda Zucker creeping (KZC) rat. In the present study, we have performed a genetic analysis of the creeping mutation, and mapped it to rat Chromosome (Chr) 4. Comparative mapping, together with the similarity of the phenotype, suggested that the creeping mutation is homologous to the mouse reeler mutation. In fact, reelin expression was markedly reduced in the homozygous mutant (cre/cre) animals compared with the normal littermates. Thus, the KZC rat should become a useful biological model with a novel mutation in the reelin gene.

Animals↗

PubMed2000

Accumulation of N-acetyl-L-aspartate in the brain of the tremor rat, a mutant exhibiting absence-like seizure and spongiform degeneration in the central nervous system.

The tremor rat is a mutant that exhibits absence-like seizure and spongiform degeneration in the CNS. By positional cloning, a genomic deletion was found within the critical region in which the aspartoacylase gene is located. Accordingly, no aspartoacylase expression was detected in any of the tissues examined, and abnormal accumulation of N-acetyl-L-aspartate (NAA) was shown in the mutant brain, in correlation with the severity of the vacuole formation. Therefore, the tremor rat may be regarded as a suitable animal model of human Canavan disease, characterized by spongy leukodystrophy that is caused by aspartoacylase deficiency. Interestingly, direct injection of NAA into normal rat cerebroventricle induced 4- to 10-Hz polyspikes or spikewave-like complexes in cortical and hippocampal EEG, concomitantly with behavior characterized by sudden immobility and staring. These results suggested that accumulated NAA in the CNS would induce neuroexcitation and neurodegeneration directly or indirectly.

Amidohydrolases↗

PubMed2000

Reflective meniscometry: a new field of dry eye assessment.

PURPOSE: To report a newly developed noninvasive method to measure the radius of tear meniscus curvature (reflective meniscometry) and its application to normal eyes, dry eyes, and other ocular surface conditions. METHODS: Two types of meniscometer--photographic and video--were devised. Both use tear meniscus as a concave mirror, and a specular reflex of an illuminated target at the meniscus was photographed or videotaped to obtain the radius of tear meniscus curvature. The photographic system was applied to 45 normal and 32 dry eyes; in the dry eyes, the radius of tear meniscus curvature was compared to the results of other dry eye examinations. The video system was used to examine meniscus formation on the ocular surface in patients with ocular surface irregularities. RESULTS: The radii of tear meniscus curvature were significantly lower in dry eyes (0.250 +/- 0.086 mm, mean +/- SD) than in normal eyes (0.365 +/- 0.153; p = 0.0003). There were significant correlations between the radius and fluorescein staining score (p = 0.0032) and the grading of interference colors on the precorneal oil film (p = 0.0125). Videomeniscometry demonstrated the tear meniscus to be very stable and proved to be useful in the study of menisci at the edge of rigid contact lenses and other menisci encountered in ocular surface disorders. CONCLUSIONS: Measurement of the radius of tear meniscus curvature may be useful in the diagnosis of dry eyes. Reflective meniscometry is expected to find wide applications in the analysis of tear meniscus in ocular surface disorders.

Diagnostic Techniques, Ophthalmological↗