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Biomedical subjects

N Maeda

Publications and source records attributed to N Maeda.

At least 235 records · Page 13Linked to original sources
PubMed1998

[Intraarterial chemotherapy using a combination of etoposide and cisplatin for recurrent malignant lymphoma].

Superselective intraarterial infusion of etoposide and cisplatin was performed in 2 patients with recurrent malignant lymphoma which had progressed after operation, radiotherapy and chemotherapy with various anticancer agents. The tip of a microcatheter (Tracker-18) was placed in the left posterior cerebral artery in the first patient with the recurrent tumor located in the left occipital lobe and at the basilar top in the second patient with the recurrent tumor extending from the right thalamus to the pons. Etoposide (60 mg) and Cisplatin (60 mg) were each infused for 1 hour safely with a combination of intermittent infusion of nicardipine and papaverine chloride. The tumor disappeared completely after 2 courses of intraarterial chemotherapy in the first patient and after 1 course in the second patient. Intraarterial chemotherapy using a combination of etoposide and cisplatin was performed safely and showed good results.

Aged↗
PubMed1998

[Effect of matrix metalloproteinase inhibitor on experimental pseudomonal corneal ulceration].

We examined the effect of matrix metalloproteinase (MMP) inhibitor (CS-610) on experimental pseudomonal corneal ulceration by clinical and histological evaluation. Intrastromal injection of 3.5 microliters sterile culture broth of P. aeruginosa, IID-1117 (13.5 unit Type I collagenase equivalent proteinase activities), was done to induce corneal ulcers in guinea pigs. The animals were divided into two groups of 23 each. The CS-610 group received topical CS-610 (400 micrograms/ml) treatment at 2-hour intervals and the control group received only the vehicle of CS-610 at the same intervals. In the control group, corneas developed acute corneal damage following corneal ulcerations at 6-12 hours. In the CS-610 group, these corneal lesions were inhibited in most of the eyes (p < 0.01). In the late period, as inflammatory cells migrated into the cornea, some animals of the CS-610 group developed corneal ulcer. The results indicated that CS-610 had a potent inhibitory activity against pseudomonal proteinases in vivo. The results also suggested that the mechanism of the ulceration model involved not only pseudomonal proteinases but also endogenous responses.

Animals↗
PubMed1997

Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A.

Natriuretic peptides, produced in the heart, bind to the natriuretic peptide receptor A (NPRA) and cause vasodilation and natriuresis important in the regulation of blood pressure. We here report that mice lacking a functional Npr1 gene coding for NPRA have elevated blood pressures and hearts exhibiting marked hypertrophy with interstitial fibrosis resembling that seen in human hypertensive heart disease. Echocardiographic evaluation of the mice demonstrated a compensated state of systemic hypertension in which cardiac hypertrophy and dilatation are evident but with no reduction in ventricular performance. Nevertheless, sudden death, with morphologic evidence indicative in some animals of congestive heart failure and in others of aortic dissection, occurred in all 15 male mice lacking Npr1 before 6 months of age, and in one of 16 females in our study. Thus complete absence of NPRA causes hypertension in mice and leads to cardiac hypertrophy and, particularly in males, lethal vascular events similar to those seen in untreated human hypertensive patients.

Animals↗
PubMed1997

Limb, genital, CNS, and facial malformations result from gene/environment-induced cholesterol deficiency: further evidence for a link to sonic hedgehog.

Low cholesterol levels produced by treating cholesterol deficient mutant mice with a cholesterol synthesis inhibitor (BM 15.766) between days 4 to 7 of pregnancy resulted in malformations consistent with those in the Smith-Lemli-Opitz syndrome (SLOS). Facial anomalies in mildly affected gestational day 12 mouse embryos included a small nose and long upper lip; in more severely affected embryos, the facial and forebrain anomalies are representative of holoprosencephaly. Additionally, abnormalities of the mid- and hind-brain were observed and included stenosis of the cerebral aqueduct at the level of the isthmus and apparent absence of the organ progenitor for the cerebellar vermis. Although not previously directly linked to cholesterol deficiency in experimental animals, limb and external genital defects were a notable outcome in this multifactorially-based cholesterol deficiency model. The results of this study provide new evidence supporting an important role for cholesterol in early embryonic development, provide additional support for the hypothesis that this role may involve the function of specific gene products, such as sonic hedgehog (shh) signaling protein, and provide a description of the pathogenesis of some of the characteristic malformations in SLOS.

Animals↗
PubMed1997

A coagulation factor IX-deficient mouse model for human hemophilia B.

Coagulation factor IX deficiency causes hemophilia B in humans. We have used gene targeting to develop a coagulation factor IX-deficient (factor IX-knockout) mouse strain. Mouse embryonic stem (ES) cells were targeted by a socket-containing vector that replaces the promoter through exon 3 of the factor IX gene by neoDeltaHPRT, which is a functional neo gene plus a partially deleted hypoxanthine phosphoribosyl transferase minigene. Chimeric mice generated using these socket-containing ES cells transmitted the targeted factor IX gene to their female offspring. Male offspring from these females were characterized and shown to exhibit a phenotype similar to hemophilia B. This factor IX-deficient mouse strain will be useful for studying gene therapy methods and structure-function relationships of recombinant factor IX proteins in vivo.

Animals↗
PubMed1997

Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2.

CC chemokine receptor 2 (CCR2) is a prominent receptor for the monocyte chemoattractant protein (MCP) group of CC chemokines. Mice generated by gene targeting to lack CCR2 exhibit normal leukocyte rolling but have a pronounced defect in MCP-1-induced leukocyte firm adhesion to microvascular endothelium and reduced leukocyte extravasation. Constitutive macrophage trafficking into the peritoneal cavity was not significantly different between CCR2-deficient and wild-type mice. However, after intraperitoneal thioglycollate injection, the number of peritoneal macrophages in CCR2-deficient mice did not rise above basal levels, whereas in wild-type mice the number of macrophages at 36 h was approximately 3.5 times the basal level. The CCR2-deficient mice showed enhanced early accumulation and delayed clearance of neutrophils and eosinophils. However, by 5 days neutrophils and eosinophils in both CCR2-deficient and wild-type mice had returned to near basal levels, indicating that resolution of this inflammatory response can occur in the absence of macrophage influx and CCR2-mediated activation of the resident peritoneal macrophages. After intravenous injection with yeast beta-glucan, wild-type mice formed numerous large, well-defined granulomas throughout the liver parenchyma, whereas CCR2-deficient mice had much fewer and smaller granulomas. These results demonstrate that CCR2 is a major regulator of induced macrophage trafficking in vivo.

Animals↗
PubMed1997

Targeted replacement of the mouse apolipoprotein E gene with the common human APOE3 allele enhances diet-induced hypercholesterolemia and atherosclerosis.

Apolipoprotein (apo) E, a constituent of several lipoproteins, is a ligand for the low density lipoprotein receptor, and this interaction is important for maintaining cholesterol and triglyceride homeostasis. We have used a gene replacement strategy to generate mice that express the human apoE3 isoform in place of the mouse protein. The levels of apoE mRNA in various tissues are virtually the same in the human apoE3 homozygous (3/3) mice and their littermates having the wild type mouse allele (+/+). Total cholesterol and triglyceride levels in fasted plasma from the 3/3 mice were not different from those in the +/+ mice, when maintained on a normal (low fat) chow diet. We found, however, notable differences in the distribution of plasma lipoproteins and apolipoprotein E between the two groups: beta-migrating lipoproteins and plasma apoB100 levels are decreased in the 3/3 mice, and the apoE distribution is shifted from high density lipoproteins to larger lipoprotein particles. In addition, the fractional catabolic rate of exogenously administered remnant particles without apoE was 6-fold slower in the 3/3 mice compared with the +/+ mice. When the 3/3 and +/+ animals were fed a high fat/high cholesterol diet, the 3/3 animals responded with a dramatic increase (5-fold) in total cholesterol compared with the +/+ mice (1.5-fold), and after 12 weeks on this same diet the 3/3 animals developed significantly (at least 13-fold) larger atherosclerotic plaques in the aortic sinus area than the +/+ animals. Thus the structural differences between human APOE3 and mouse ApoE proteins are sufficient to cause an increased susceptibility to dietary-induced hypercholesterolemia and atherosclerosis in the 3/3 mice.

Alleles↗
PubMed1997

Inactivation of the mouse HPRT locus by a 203-bp retroposon insertion and a 55-kb gene-targeted deletion: establishment of new HPRT-deficient mouse embryonic stem cell lines.

To obtain useful hypoxanthine phosphoribosyl-transferase (HPRT)-deficient mouse ES cell lines, two different methods were employed: (i) selection of spontaneous 6-TG-resistant mutants and (ii) gene targeting of the HPRT locus. The first approach resulted in the establishment of E14.1TG3B1, a spontaneous HPRT-deficient cell line with an insertional mutation of 203 bp in the third exon of the HPRT gene. The insert is highly homologous to the B2 mouse repetitive element and has all the expected retroposon characteristics, thus providing an example of gene inactivation by retroposon insertion. This clone exhibited stable 6-TG resistance and high germ-line transmission frequency. Thus E14.1TG3B1 is a useful ES cell line for modifying the mouse genome using the HPRT gene as a selection marker and for transmission at a high frequency into the mouse germ line. The second approach resulted in a 55-kb deletion of the mouse HPRT locus, demonstrating the feasibility of replacement-targeting vectors to generate large genomic DNA deletions.

Animals↗
PubMed1997

Paradoxical enhancement of atherosclerosis by probucol treatment in apolipoprotein E-deficient mice.

Dietary administration of probucol (0.5%, wt/wt) efficiently reduced total plasma cholesterol levels in apolipoprotein E-deficient mice (apoE-/-) by 40%, with decreases in high density lipoprotein (HDL) and apoAI by 70 and 50%, respectively. Paradoxically, however, aortic atherosclerotic plaques in the probucol-treated apoE-/- mice formed more rapidly than in the untreated apoE-/- mice, and the lesions were two to four times larger and more mature regardless of sex, age, and genetic background (P < 10(-)6). Histologically, lesions in probucol-treated mice contained increased fibrous materials and cells other than foam cells, and were commonly associated with focal inflammation and aneurysmal dilatation. Probucol treatment also accelerated lesion development in apoE+/- mice fed an atherogenic diet, indicating that the adverse effect is not dependent on the complete absence of apoE. Furthermore, mice lacking apoE and apoAI have plasma lipoprotein profiles very similar to the probucol-treated apoE-/- mice, but do not have accelerated plaque development. Thus, the enhanced atherosclerosis in the probucol-treated animals is unlikely to be caused by the reduction of HDL and apoAI levels. Our data indicate that a reduction in plasma cholesterol caused by probucol does not necessarily lead to an antiatherogenic effect.

Animals↗
PubMed1997

Hepatic lipase deficiency increases plasma cholesterol but reduces susceptibility to atherosclerosis in apolipoprotein E-deficient mice.

The effect of hepatic lipase (HL) deficiency on the susceptibility to atherosclerosis was tested using mice with combined deficiencies in HL and apoE. Mice lacking both HL and apoE (hhee) have a plasma total cholesterol of 917 +/- 252 mg/dl (n = 24), which is 184% that of mice lacking only apoE (HHee; 497 +/- 161 mg/dl, n = 20, p < 0. 001). The increase in cholesterol was mainly in beta-migrating very low density lipoproteins, although high density lipoprotein cholesterol (HDLc) was also increased (53 +/- 37 versus 20 +/- 13 mg/dl, p < 0.01). Despite the increase in plasma cholesterol, we found that HL deficiency significantly decreased aortic plaque sizes in female mice fed normal chow (31 x 10(3) +/- 22 x 10(3) microm2 in hhee versus 115 x 10(3) +/- 69 x 10(3) microm2 in HHee, p < 0.001). Reduction of plaque sizes was also observed in female heterozygous apoE-deficient mice fed an atherogenic diet (2 x 10(3) +/- 2.5 x 10(3) microm2 in hhEe versus 56 x 10(3) +/- 49 x 10(3) microm2 in HHEe, p < 0.01). Changes in aortic lesion size were not apparent in the small number of male mice studied. In HHee females, both HDLc and the capacity of high density lipoprotein (HDL) particles to promote cholesterol efflux from cultured cells were 26% of the wild type. The absence of HL in hhee females partially restored HDLc levels to 57% and cholesterol efflux to 55% of the wild type. Circulating pre-beta1-migrating HDL were present in all mutants, suggesting that there are alternative pathways in the formation of these pre-beta-HDL not involving apoE, HL, or cholesteryl ester transfer protein. The improved capacity to promote cholesterol efflux, together with increased HDL, may explain why these animals can overcome the increase in atherogenic lipoproteins.

Animals↗
PubMed1997

Gastrointestinal absorption of insulin-like growth factor in the mouse in the absence of salivary insulin-like growth factor binding protein.

Based on previous observations of the presence of both insulin-like growth factors I and II (IGF-I and IGF-II) in murine saliva (kerr et al., Biochem Pharmacol 49: 1521-1531, 1995), the saliva from BALB/c and Non-obese diabetic (NOD) mice was examined for the presence of insulin-like growth factor binding proteins (IGFBPs). Using a western-blot type ligand binding assay with 125I-labeled IGF-I, a series of binding proteins with molecular masses (M), between 25 and 45 kDa were detected in the sera, but not saliva, from both BALB/c and diabetic NOD mice. In the diabetic NOD mice, there were detectable changes in the concentrations of several of the IGFBPs relative to BALB/c mice. Using specific antibody to the binding proteins, one of these was identified as IGFBP-2. Gavage administration of [125I]IGFI indicated substantial uptake from the gastrointestinal tract and significant tissue distribution. There was an increase in serum concentrations of radiolabeled IGF-I in diabetic NOD mice over that in BALB/c mice but less recovered from most of the tissues. Intact 125I-labeled IGF-I was extracted and purified from various tissues, following gavage, and shown to retain biological activity. Thus, the uptake of biologically active IGFs from saliva would appear to take place independently of specific binding proteins.

Animals↗
PubMed1997

Characterization of rat receptor-like protein tyrosine phosphatase gamma isoforms.

We identified four isoforms of receptor-like protein tyrosine phosphatase gamma (RPTPgamma) from rat brain by cDNA cloning. We designated these molecules RPTPgamma-A, -B, -C, and -S. RPTPgamma-A was the longest form and had the same structure as human and mouse RPTPgamma. RPTPgamma-B lacked the intracellular juxtamembrane 29 amino acids of RPTPgamma-A. RPTPgamma-C had a single phosphatase domain. RPTPgamma-S is an extracellular variant of RPTPgamma. mRNAs of the four isoforms were expressed in the brain, kidney, lung, and heart. Transfection of RPTPgamma-A and -S expression plasmids into COS7 cells resulted in the expression of membrane-bound 190-kDa proteins and secreted 120-kDa proteins, respectively. These molecules were similar to PTPzeta/RPTPbeta with regard not only to structure but also to the presence of both secretory and transmembrane forms. However, RPTPgamma isoforms were not expressed as proteoglycans.

Amino Acid Sequence↗
PubMed1997

Expression of a mucin-like glycoprotein produced by ocular surface epithelium in normal and keratinized cells.

PURPOSE: We previously characterized a monoclonal antibody (H185) to a mucin-like glycoprotein produced by human ocular surface epithelium. In the current study, we used H185 to investigate the pattern of the mucin-like glycoprotein in normal and keratinized apical cells of the ocular surface epithelium. METHODS: We compared the cell characteristics and the pattern of H185 binding in cytologically and immunohistochemically stained samples of apical cells of conjunctival surface epithelium from 20 normal subjects and six patients before and after treatment for superior limbic keratoconjunctivitis. RESULTS: In the superior bulbar conjunctiva of normal subjects, the intensity with which H185 antibody bound to apical surface epithelial cells varied, with areas of high-, medium-, and low-intensity binding occurring in a mosaic pattern. This mosaic pattern, and presumably expression of the mucin-like glycoprotein, was absent or remarkably reduced in keratinized cells obtained from patients with superior limbic keratoconjunctivitis before treatment. However, the pattern of H185 binding was normal in samples obtained 2 months after the start of treatment for superior limbic keratoconjunctivitis, and cells had recovered their normal small, round appearance. CONCLUSION: When they are keratinized, apical cells of the ocular surface epithelium are altered in appearance and lack the normal mosaic pattern of expression of a mucin-like glycoprotein.

Administration, Topical↗
PubMed1997

Unilateral keratoconus. Incidence and quantitative topographic analysis.

OBJECTIVE: This study was designed to determine the incidence of unilaterality in a population of patients with clinical keratoconus and to compare quantitative descriptors of topography between affected corneas from patients with unilateral keratoconus and corneas of patients with bilateral disease. DESIGN: Retrospective clinical study with new evaluation of some patients. PARTICIPANTS: One hundred sixty-four patients from the University of Texas South-western Medical Center and Wills Eye Hospital who were diagnosed to have moderate-to-advanced keratoconus on the basis of characteristic topographic patterns associated with corneal thinning. INTERVENTION: Corneal topography was evaluated in both eyes of each patient. MAIN OUTCOME MEASURES: Quantitative descriptors of corneal topography were compared between 5 affected corneas of patients with unilateral keratoconus (combined cases from University of Texas Southwestern, LSU Eye Center, and Wills Eye Hospital) and 15 corneas of patients with moderate-to-advanced bilateral keratoconus (1 cornea from each patient). Indices selected for statistical analysis were the Keratoconus Predication Index (KPI), Surface Asymmetry Index (SAI), and Surface Regularity Index (SRI). RESULTS: Three (1.83%) of 164 patients with moderate-to-advanced keratoconus had no topographic evidence of keratoconus in the opposite eye. There were no statistically significant differences in KPI, SRI, or SAI values between the affected corneas of patients with unilateral and bilateral keratoconus. Over a period of 4 years of observation, signs of keratoconus in the previously normal eye developed in a patient with unilateral keratoconus. CONCLUSIONS: The authors found no differences in the quantitative descriptors of corneal topography between corneas with keratoconus from unilateral and bilateral cases. The authors' results suggest that the incidence of "unilateral" keratoconus is very low. Patients initially diagnosed with unilateral keratoconus, if observed for a sufficient period, commonly had signs of keratoconus develop in the opposite eye. The possibility that all cases of unilateral keratoconus may eventually become bilateral cannot be excluded. Therefore, refractive surgical procedures should not be performed on apparently normal corneas when keratoconus is detected in the opposite eye.

Cornea↗
PubMed1997

Protection of ischemic hippocampal neurons by ginsenoside Rb1, a main ingredient of ginseng root.

Our previous study showed that the oral administration of red ginseng powder before but not after transient forebrain ischemia prevented delayed neuronal death in gerbils, and that a neuroprotective molecule within red ginseng powder was ginsenoside Rb1. However, it remains to be clarified whether or not ginsenoside Rb1 acts directly on the ischemic brain, and the mechanism by which ginsenoside Rb1 protects the ischemic CA1 neurons is not determined. Without elucidation of the pharmacological property of ginsenoside Rb1, the drug would not be accepted as a neuroprotective agent. The present study demonstrated that the intracerebroventricular infusion of ginsenoside Rb1 after 3.5 min or 3 min forebrain ischemia, precluded significantly the ischemia-induced shortening of response latency in a step-down passive avoidance task and rescued a significant number of hippocampal CA1 neurons from lethal ischemic damage. The intracerebroventricular infusion of ginsenoside Rb1 did not affect hippocampal blood flow or hippocampal temperature except that it caused a slight increase in hippocampal blood flow at 5 min after transient forebrain ischemia. Furthermore, ginsenoside Rb1 at concentrations of 0.1-100 fg/ml (0.09-90 fM) rescued hippocampal neurons from lethal damage caused by the hydroxyl radical-promoting agent FeSO4 in vitro, and the Fenton reaction system containing p-nitrosodimethylaniline confirmed the hydroxyl radical-scavenging activity of ginsenoside Rb1. These findings suggest that the central infusion of ginsenoside Rb1 after forebrain ischemia protects hippocampal CA1 neurons against lethal ischemic damage possibly by scavenging free radicals which are overproduced in situ after brain ischemia and reperfusion. The present study may validate the empirical usage of ginseng root over thousands of years for the prevention of cerebrovascular diseases.

Animals↗