Search PubMed⌕ Search

Biomedical subjects

N Maeda

Publications and source records attributed to N Maeda.

At least 217 records · Page 12Linked to original sources
PubMed1998

Topographic assessment of irregular astigmatism after photorefractive keratectomy.

OBJECTIVE: To correlate new quantitative topographic indexes of corneal irregular astigmatism to best spectacle-corrected visual acuity (BSCVA) following excimer laser photorefractive keratectomy (PRK). SETTING: Department of Ophthalmology, LSU Eye Center, and Refractive Surgery Center of the South, Ear, Nose & Throat Hospital, New Orleans, Louisiana; Manhattan Eye, Ear and Throat Hospital, New York, New York, USA. METHODS: Videokeratography data (TMS-1) were obtained preoperatively and 1, 3, 6, 12, 18, and 24 months postoperatively from 100 eyes having PRK for low to mild myopia. Algorithms measured fine local irregularity with the surface regularity index (SRIp), varifocality with the coefficient of variation of corneal power (CVPp), and central islands with the elevation/depression magnitude (EDM). RESULTS: The SRIp and CVPp increased after surgery and remained significantly higher than the preoperative levels throughout the 24 month follow-up (P < .05). The increase in EDM was significant from 1 to 6 months (P < .05) but not thereafter. Multiple regression analysis revealed that variables having a statistically significant relationship with postoperative BSCVA were CVPp and EDM at 1 month, CVPp at 3 months, and CVPp, haze, and age at 6 months. No statistically significant correlation between any measures of irregular astigmatism and BSCVA was found after 1 year of follow-up. CONCLUSION: The quantitative measures used in this study are sensitive methods by which irregular astigmatism after keratorefractive procedures can be classified, evaluated, and compared.

Algorithms↗
PubMed1998

Complications in wrap-around-flap donor sites after reconstruction using an arterialized venous flap.

The authors have previously reported on the use of the arterialized venous flap to cover skin defects of the big toe resulting from wrap-around-flap transfers. Nineteen patients who had undergone this procedure were reviewed, to determine the incidence of donor-site complications. Problems identified included delayed wound healing, skin erosion, painful callosity, paresthesia, cold intolerance, and cosmetic appearance However, the functional deficit was not great, and most patients were not troubled by their symptoms. The cosmetic appearance of the donor foot was acceptable in most of the patients.

Adolescent↗
PubMed1998

Homozygosity mapping of a gene responsible for gelatinous drop-like corneal dystrophy to chromosome 1p.

Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive disorder characterized clinically by grayish corneal deposits of amyloid and by severely impaired visual acuity. Most patients require corneal transplantation. To localize a gene responsible for GDLD, we performed linkage analysis of 10 consanguineous Japanese families with a total of 13 affected members. Homozygosity mapping provided a maximum LOD score of 9.80 at the D1S2741 marker locus on the short arm of chromosome 1. Haplotype analysis further defined the disease locus within a region of approximately 2.6 cM between D1S2890 and D1S2801.

Chromosome Mapping↗
PubMed1998

Characterization and developmental regulation of proteoglycan-type protein tyrosine phosphatase zeta/RPTPbeta isoforms.

Protein tyrosine phosphatase zeta (PTPzeta/RPTPbeta) is a receptor-like protein tyrosine phosphatase specifically expressed in the brain. Alternative splicing produces three isoforms of this molecule: PTPzeta-A, the full-length form of PTPzeta; PTPzeta-B, the short form of PTPzeta; and PTPzeta-S, an extracellular variant. Here, we identified all these isoforms, including PTPzeta-B, as chondroitin sulfate proteoglycans, and characterized their carbohydrate modification and expression profiles in the rat brain. The level of PTPzeta-A expression was maintained during the prenatal period and decreased rapidly after birth. PTPzeta-S was expressed in a similar manner, although the postnatal decrease was gradual. In contrast, relatively constant amounts of PTPzeta-B were observed from embryonic day 13 (E13) through adulthood. PTPzeta-A and -S were constantly expressed only as proteoglycans during development, but a substantial amount of PTPzeta-B was detected in a non-proteoglycan form at E13-15. Moreover, PTPzeta-B did not contain LeX, HNK-1 carbohydrate, or keratan sulfate, although PTPzeta-A and -S were generally modified with these carbohydrates. L cells transfected with PTPzeta-A and -B cDNAs expressed these proteins as enzymatically active chondroitin sulfate proteoglycans. The PTPzeta-A and -B in L cells showed essentially similar localizations in cell cortical structures on immunofluorescence microscopy, although immature or processed forms of PTPzeta-A were accumulated additively in intracellular patchy structures. These results show that the three isoforms of PTPzeta are differentially regulated during development, and that the extracellular deleted region in PTPzeta-B is important for determination of carbohydrate modification.

Animals↗
PubMed1998

Epidermal growth factor protects neuronal cells in vivo and in vitro against transient forebrain ischemia- and free radical-induced injuries.

Epidermal growth factor (EGF) has been considered to be a candidate for neurotrophic factors on the basis of the results of several in vitro studies. However, the in vivo effect of EGF on ischemic neurons as well as its mechanism of action have not been fully understood. In the present in vivo study using a gerbil ischemia-model, we examined the effects of EGF on ischemia-induced learning disability and hippocampal CA1 neuron damage. Cerebroventricular infusion of EGF (24 or 120 ng/d) for 7 days to gerbils starting 2 hours before or immediately after transient forebrain ischemia caused a significant prolongation of response latency time in a passive avoidance task in comparison with the response latency of vehicle-treated ischemic animals. Subsequent histologic examinations showed that EGF effectively prevented delayed neuronal death of CA1 neurons in the stratum pyramidale and preserved synapses intact within the strata moleculare, radiatum, and oriens of the hippocampal CA1 region. In situ detection of DNA fragmentation (TUNEL staining) revealed that ischemic animals infused with EGF contained fewer TUNEL-positive neurons in the hippocampal CA1 field than those infused with vehicle alone at the seventh day after ischemia. In primary hippocampal cultures, EGF (0.048 to 6.0 ng/mL) extended the survival of cultured neurons, facilitated neurite outgrowth, and prevented neuronal damage caused by the hydroxyl radical-producing agent FeSO4 and by the peroxynitrite-producing agent 3-morpholinosydnonimine in a dose-dependent manner. Moreover, EGF significantly attenuated FeSO4-induced lipid peroxidation of cultured neurons. These findings suggest that EGF has a neuroprotective effect on ischemic hippocampal neurons in vivo possibly through inhibition of free radical neurotoxicity and lipid peroxidation.

Animals↗
PubMed1998

Incidence of Prevotella intermedia and Prevotella nigrescens in periodontal health and disease.

The incidence of black-pigmented rods (BPRs), especially Prevotella intermedia and Prevotella nigrescens, in periodontal health and disease were examined. Furthermore, the degradative enzyme activities of P. intermedia were compared among the strains from periodontal health and disease. Microbiological specimens were collected from subgingival crevice or periodontal pocket by paper point. The BPRs were found in 71.1% of periodontally healthy subjects (n=45), and in 47.1% of healthy sites (n=34) and 87.8% of active sites (n=41) among periodontally diseased patients. Porphyromonas gingivalis was detected only in active sites of periodontally diseased patients (17.8% of 180 strains). P. intermedia was the predominant BPR in both healthy and active sites (37.3 and 41.7%, respectively) of the patients. However, P. nigrescens was the predominant BPR (70.5% of 173 strains) in periodontally healthy subjects. The enzyme activities of esterase, esterase-lipase, acid-phosphatase and alpha-fucosidase of P. intermedia strains isolated from active sites in patients were significantly higher (P<0.05) than those of healthy subjects. The results suggest that P. intermedia might increase the activity of degradative enzymes under a certain condition and support the progression of periodontitis.

Adult↗
PubMed1998

Transmission of human T-cell leukemia virus type 1 to mice.

Human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis, and other diseases. For prevention of the transmission of HTLV-1 and manifestation of these diseases, a small-animal model, especially a mouse model, would be useful. We injected HTLV-1-producing T cells (MT-2) intraperitoneally into neonatal C3H/HeJ mice. While the antibody against HTLV-1 antigens was not detectable in C3H/HeJ mice, HTLV-1 provirus was frequently detected in the spleen, lymph nodes, and thymus by PCR. HTLV-1 provirus was present at the level of 0 to 30 molecules in 10(5) spleen cells at the age of 15 weeks. In addition, a 59-bp flanking sequence of the HTLV-1 integration site was amplified from the spleen DNA by linker-mediated PCR and was confirmed to be derived from the mouse genome. HTLV-1 provirus was found in the T-cell fraction of the mouse spleen. These results indicate that mice can be infected by HTLV-1 and could serve as an animal model for the study of HTLV-1 infection and its pathogenesis in vivo.

Animals↗
PubMed1998

Responses of carotid artery in mice deficient in expression of the gene for endothelial NO synthase.

We examined the hypotheses that responses to acetylcholine are impaired and responses to NO are enhanced in carotid artery from mice made deficient in endothelial nitric oxide synthase (eNOS) by gene targeting (eNOS-deficient mice). We also tested the hypothesis that deletion of one copy of the eNOS gene is sufficient to alter vascular responses. Vessels were studied in vitro from heterozygous (+/-) and homozygous (-/-) eNOS-deficient mice as well as wild-type [eNOS(+/+)] littermates. After precontraction with prostaglandin F2 alpha, acetylcholine produced marked relaxation of carotid arteries in eNOS(+/+) mice, with impaired vasorelaxation in eNOS(+/-) mice. For example, 1 microM acetylcholine relaxed carotid arteries by 55 +/- 5% (mean +/- SE) in eNOS(+/-) mice (n = 13) compared with 83 +/- 3% in eNOS(+/+) mice (n = 14, P < 0.001 vs. +/-). In contrast, acetylcholine caused no relaxation in carotid arteries from eNOS(-/-) mice (P < 0.001 vs. +/+ and +/-). Relaxation of the carotid artery in response to nitroprusside [a nitric oxide (NO) donor] was enhanced (P < 0.001) in eNOS-deficient mice. For example, in response to 10 nM nitroprusside, the carotid artery relaxed by 18 +/- 2% in eNOS(+/+) mice (n = 14), 33 +/- 2% in eNOS(+/-) mice (n = 13), and 47 +/- 4% in eNOS(-/-) mice (n = 5). Thus relaxation of the carotid artery is impaired with acetylcholine and enhanced with the NO donor nitroprusside in eNOS-deficient mice. Enhanced responses to NO may represent a compensatory response expressed in the absence of eNOS. The findings that vascular responses to acetylcholine and NO are altered in eNOS(+/-) mice compared with those observed in eNOS(+/+) mice suggest a "gene-dosing" effect.

Acetylcholine↗
PubMed1998

Renal growth and development in mice lacking AT1A receptors for angiotensin II.

To examine the role of the type 1A (AT1A) angiotensin receptor in renal growth and development, we analyzed F2 progeny from a series of crosses between F1 mice that were heterozygous for a targeted disruption of the AT1A receptor gene [Agtr1A-(+/-)]. Among 21-day-old weanling F2 mice, we found that 194 (32%) were homozygous for the wild-type allele Agtr1A-(+/+), 299 (49%) were Agtr1A-(+/-), and 119 (19%) were Agtr1A-(-/-). This differed significantly from the proportions predicted by Mendelian genetics (P = 0.01), suggesting that the complete absence of AT1A receptors is associated with a mild survival disadvantage. Agtr1A-(-/-) mice grew normally, and we found no significant differences in body weight or heart and kidney weights in Agtr1A-(+/+) and Agtr1A-(-/-) mice examined at 21, 60, and 100 days. Protein and DNA content of kidneys and hearts were also similar in weanling or adult Agtr1A-(+/+) and Agtr1A-(-/-) mice. By light microscopy with immunohistochemistry, kidneys from Agtr1A-(-/-) were essentially normal, with two exceptions: 1) there was marked hypertrophy of the juxtaglomerular apparatus (JGA) and proximal expansion of renin-producing cells along the afferent arterioles, and 2) some glomeruli showed evidence of mesangial expansion. We did not find the severe renal vascular lesions or papillary atrophy that have been observed in angiotensinogen- or angiotensin converting enzyme-deficient animals. We conclude that the AT1A receptor is not essential for the normal organogenesis of the kidney; however, its absence is associated with mild mesangial expansion and JGA hypertrophy.

Angiotensin II↗
PubMed1998

Angiotensin AT1B receptor mediates calcium signaling in vascular smooth muscle cells of AT1A receptor-deficient mice.

Our studies on angiotensin II receptor subtype 1A (AT1A) knockout mice define how endogenous receptors other than AT1A receptors stimulate changes in cytosolic calcium concentration ([Ca2+]i) in cultured aortic vascular smooth muscle cells (VSMCs). Wild-type cells have a 1.7 ratio of AT1A/AT1B receptor mRNA as determined by semiquantitative reverse transcriptase-polymerase chain reaction. Mutant cells express AT1B receptor mRNA but not that for the AT1A receptor. In wild-type cells with AT1A present, Ang II (10(-7) mol/L) produces a characteristic rapid peak increase in [Ca2+]i of 150 to 180 nmol/L, followed by a plateau phase characterized by a sustained 70 to 80 nmol/L increase in [Ca2+]i. An unexpected finding was that the magnitude and time-dependent pattern of [Ca2+]i changes produced by Ang II were similar in cells that lacked AT1A receptors but possessed AT1B receptors. The response in mutant cells indicates effective coupling of an Ang II receptor to one or more second messenger systems. The similarity of response patterns between cells with and without AT1A receptors suggests that non-AT1A receptors are functionally linked to similar signal transduction pathways in mutant cells. The fact that mutant and wild-type cells exhibit similar patterns of calcium mobilization and entry supports the notion that AT1A and non-AT1A receptors share common signal transduction pathways. The AT2 receptor ligands PD-123319 and CGP-42112 do not alter Ang II effects in either VSMC type, suggesting a paucity of AT2 receptors and/or an absence of their linkage to [Ca2+]i pathways. The nonpeptide AT1 receptor blocker losartan antagonizes Ang II-induced [Ca2+]i increases in both cell groups, supporting mediation by native AT1B receptors and effective coupling of this subtype to second messenger systems leading to calcium entry and mobilization. Our results demonstrate that Ang II causes calcium signaling in AT1A-deficient VSMCs that is mediated by an endogenous losartan-sensitive AT1B receptor.

Angiotensin II↗
PubMed1998

[The effect of matrix metalloproteinase inhibitor on pseudomonal proteinases].

We examined the effect of CS-610, a newly developed matrix metalloproteinase (MMP) inhibitor, on pseudomonal proteinase in vitro. Alkaline proteinase (1143-4977 unit/ml Type I collagenase equivalent) and elastase (13.6-22.6 unit/ml Type I collagenase equivalent) were obtained from strains of P. aeruginosa of IID-1117, IID-1030 and IID-1130. Zymographic analysis of cultured broth of P. aeruginosa demonstrated that CS-610 inhibited alkaline proteinase with an IC50 (50% inhibition concentration) of 1.06-29.0 (x 10(-8)M) and elastase with an IC50 of 1.0-33.3 (x 10(-8)M). CS-610 is a potent inhibitor of pseudomonal proteinases.

Dose-Response Relationship, Drug↗
PubMed1998

[Drug delivery system (DDS) for the use of antisense oligodeoxynucleotide phosphorothioate in controlling gene expression].

Synthetic antisense oligodeoxynucleotide phosphorothioates (ODNs) are widely used as therapeutic tools in various in vitro and in vivo systems. Here, we applied ODNs to inhibit viral gene expression. Human T-cell leukemia virus type I (HTLV-I) is a retrovirus, and is closely linked to adult T-cell leukemia (ATL), HTLV-I-associated myelopathy/tropical spastic paraparesis(HAM/TSP), and other HTLV-I-associated diseases. With an attempt to control viral replication in vitro, ODNs to HTLV-I tax gene were synthesized and applied. In addition, 1,2-dioleoyloxy-3-(trimethylammonio) propane, DOTAP as a drug delivery system, was exploited to increase the cellular uptake of ODNs. Combination of ODNs and DOTAP was more effective to suppress viral antigen expression than ODNs only. Therefore this combination method may be useful in clinical trials for HTLV-I-associated diseases.

Drug Carriers↗
PubMed1998

Severe corneal dystrophy phenotype caused by homozygous R124H keratoepithelin mutations.

PURPOSE: To determine the mutational status of the beta ig-h3 gene in five patients from four Japanese families affected with an unusual, severe form of corneal dystrophy. In these five cases, the corneas were remarkable for confluent round opacities in the superficial stromal layer. The beta ig-h3 gene coding for keratoepithelin was recently identified as the gene responsible for 5q-linked autosomal dominant corneal dystrophies. METHODS: Genomic DNA was isolated from leukocytes of five patients with the severe form of corneal dystrophy. To screen for point mutations, exons of the beta ig-h3 gene were amplified by polymerase chain reaction and were analyzed with the single-strand conformational polymorphism technique. Subsequently, the mutations were identified by a direct sequencing method and restriction enzyme digestion analysis. RESULTS: All five patients with the severe form of corneal dystrophy had homozygous R124H keratoepithelin mutations. Histopathologic examinations of the corneas obtained from two patients with the severe form showed granular, rod-shaped deposits. CONCLUSIONS: The severe phenotype was a pathologic variant of granular corneal dystrophy (GCD). All five patients had homozygous R124H keratoepithelin mutations. The R124H keratoepithelin mutation is the same mutation recently reported to be responsible for Avellino corneal dystrophy. The homozygous R124H keratoepithelin mutations are the cause of the severe variant of GCD characterized by juvenile-onset and confluent superficial opacity.

Adult↗
PubMed1998

Induction of resting microglia in culture medium devoid of glycine and serine.

Cultured microglial cells usually exhibit ameboid morphology and peripheral macrophage-like properties, which are distinct from those observed in the normal mature brain. This might be caused by the inappropriate culture of microglial cells in high concentrations (approximately 200-400 microM) of Gly and Ser, although the concentrations of the amino acids in extracellular spaces of the brain parenchyma are quite low (approximately 5 microM). In the present study, we focused on the concentration-dependent effects of glycine (Gly) and serine (Ser) on microglial morphology and function. Under Gly/Ser-free and serum-free condition, the majority of rat microglial cells displayed round morphology, whereas in the presence of 5 microM Gly and 25 microM Ser, which correspond to the concentrations of Gly and Ser in the cerebrospinal fluid, they extended multiple branched processes and formed clusters of rough endoplasmic reticulum. On the other hand, Gly and Ser did not affect morphology of astrocytes. The viability of microglia was not affected by the changes in the concentrations of Gly and Ser. Metabolic activity, activities of acid phosphatase and inducible nitric oxide synthase, and superoxide anion (O2-) generation were all strongly suppressed in Gly/Ser-free medium or in medium containing physiological concentrations of both amino acids. Such activities were all enhanced in harmony with increases in the concentrations of Gly and Ser. Thus, microglial cells cultured in Gly/Ser-free medium, even though exhibiting ameboid morphology, appears to be in the functionally resting state. Furthermore, once the resting state was achieved, the microglial cells remained inactive even after the subsequent 24 h culture in serum-supplemented medium containing 400 microM of both amino acids. The medium conditioned by microglial cells that were cultured in the presence of 400 microM of Gly and Ser was toxic to cortical neurons, whereas the microglia-conditioned medium obtained in the absence of both amino acids facilitated the survival of cortical neurons. Therefore, microglial cells in the resting state, which was induced in the Gly/Ser-free condition, are likely to support neurons. Microglial cells could ramify on glass coverslips coated with astrocyte-derived extracellular matrix or on coverslips coated thinly with fibronectin and/or laminin even under the Gly/Ser-free condition. The ramified cells as induced in this way kept suppressed O2- generating activity. These findings suggest that resting ramified microglial cells with a neurotrophic activity can be induced with the combination of Gly/Ser-free medium and small amounts of extracellular matrix proteins, and that the resting state is rather stable.

Acid Phosphatase↗
PubMed1998

Salivary gland changes in the NOD mouse model for Sjögren's syndrome: is there a non-immune genetic trigger?

Sjögren's syndrome is a systemic autoimmune disease characterized by patient complaints of oral and ocular dryness accompanied by clinical observations of a progressive loss of salivary and lacrimal function, related to the presence of a focal, periductal leukocyte infiltrate. Progress in understanding the mechanisms involved in the development of autoimmune diseases in general, and Sjögren's syndrome specifically, has been generated as a result of renewed interest in animal models, such as the NOD mouse, which mimics autoimmune sialoadenitis. Biochemical analyses have indicated that the salivary glands have reduced beta-adrenergic, muscarinic, and neuropeptide signal transduction responses that correlate to reduced receptor density and the appearance of autoantibodies directed against these and other cell surface proteins. Using the NOD-scid mouse (lacking functional B- and T-lymphocytes) it has been determined that salivary flow rates are normal; however, these animals show abnormal changes in protein biosynthesis with increasing age. Histological evaluation of the submandibular gland from older NOD-scid mice revealed a loss of acinar cells accompanied by a potential increase in the ductal cell component of the tissue. Consistent with this finding, we recently have observed increased levels of cell death-associated cysteine proteases in the submandibular glands of 20 week NOD and NOD-scid mice but not in BALB/c and young NOD controls. Other novel protease activity was detected in the parotid and submandibular glands from NOD mice, which were able to generate the aberrantly processed PSP from purified BALB/c protein. Taken together, these data paint a complex picture of the development of Sjögren's syndrome-like disease in the NOD mouse model. The presence of activated lymphocytes appears to be necessary for the ultimate loss of exocrine gland function, potentially through the loss of tolerance to glandular proteins. However, the findings of high levels of apoptosis and aberrant protein expression in the submandibular gland in the absence of an immune response (NOD-scid) suggests that genetic alterations in glandular homeostasis involving the death program contribute to disease progression or even the initial trigger of autoimmunity.

Animals↗
PubMed1998

[Clinical application of FdUrd to meningeal dissemination of malignant tumors].

A clinical trial of intrathecal chemotherapy with FdUrd was performed in sixteen patients with meningeal dissemination of malignant tumors. Twelve of the sixteen patients responded to intrathecal FdUrd chemotherapy (1-5 micrograms/dose) through an Ommaya reservoir placed in the lateral ventricle: complete response, 2; partial response, 10; progressive disease, 4. Only slight nausea was observed in two patients and dull headache in one patient. No other systemic side effects such as myelosuppression or liver dysfunction were observed in any patients. Moreover, no delayed side effects such as marked brain atrophy or leukoencephalopathy developed during the course of this intrathecal chemotherapy despite over thirty consecutive intrathecal administrations. In conclusion, intrathecal FdUrd proved to be safe and effective for the treatment of meningeal dissemination of malignant tumors.

Adenocarcinoma↗