Biomedical subjects

J Nakabayashi

Publications and source records attributed to J Nakabayashi.

6 recordsLinked to original sources

PubMed2001

Visualization of endogenous BMP signaling during Xenopus development.

The TGF-beta superfamily of growth factors is known to transmit signals to the nucleus mainly through the Smads, intracellular signaling components that are highly conserved from nematodes to humans. The signaling activity of the Smads is regulated by their ligand-stimulated phosphorylation through Ser/Thr kinase receptors. Here, to examine the in vivo role of BMP, we investigated the spatio-temporal activation of BMP-regulated signals during Xenopus development, using a polyclonal antibody that specifically recognizes the phosphorylated form of BMP-regulated Smads. BMP signaling was observed uniformly in embryos as early as stage 7, but was restricted to the ventral side of the embryo at the late blastula stage, supporting the proposed role of BMP4 as a ventralizing factor in Xenopus embryos. In addition, localized staining was detected in several developing organs, consistent with the predicted function of BMP family members in organogenesis.

Animals↗

PubMed2000

Role of blood vessels in producing pathological changes in the brain with Alzheimer's disease.

Vascular factors have been shown to be highly involved in the deposition of the amyloid beta-protein (A beta) in the brain of Alzheimer's disease (AD). However, the detailed mechanism remains unknown. Here, we showed that more numerous deposits of A beta 40 and A beta 42 in the brain were found in AD patients than in controls. Together with evidence of no difference in the level of A beta 40 and A beta 42 in sera between sporadic AD and controls, a certain dysfunction of the blood-brain barrier could induce an abnormal transport of A beta from sera to the parenchyma in AD. In addition, vascular A beta deposits and mature A beta plaques stained by Congo red in AD brains contained more A beta 40 than A beta 42, whereas Congo red-negative immature plaques mainly consisted of A beta 42. Our confocal laser scanning microscopy demonstrated an intimate relationship between A beta 40 and the vascular network. The amount of mature plaques but not that of immature plaques was reportedly correlated with the severity of dementia in AD patients. These results suggest that serum-derived A beta 40 and/or A beta 42 cause A beta 40 deposition in and around blood vessels through unknown but possible mechanisms such as (1) endocytosis of A beta 40, (2) selective transport A beta 40 and A beta 42 into blood vessels and the parenchyma, respectively, and (3) proteolysis of A beta 42 into A beta 40 induced by a putative carboxyl dipeptidase in blood vessels including vascular feet, which is involved in A beta fibrillation and cognitive deterioration in the patients. Therefore, the accumulation of A beta 40 associated with blood vessels may play a critical role in the development of AD.

Aged↗

PubMed1999

Functional equivalency between Otx2 and Otx1 in development of the rostral head.

Mice have two Otx genes, Otx1 and Otx2. Prior to gastrulation, Otx2 is expressed in the epiblast and visceral endoderm. As the primitive streak forms, Otx2 expression is restricted to the anterior parts of all three germ layers. Otx1 expression begins at the 1 to 3 somite stage in the anterior neuroectoderm. Otx2 is also expressed in cephalic mesenchyme. Otx2 homozygous mutants fail to develop structures anterior to rhombomere 3 (r3), and Otx2 heterozygotes exhibit craniofacial defects. Otx1 homozygous mutants do not show apparent defects in early brain development. In Otx1 and Otx2 double heterozygotes, rostral neuroectoderm is induced normally, but development of the mes/diencephalic domain is impaired starting at around the 3 to 6 somite stage, suggesting cooperative interactions between the two genes in brain regionalization. To determine whether Otx1 and Otx2 genes are functionally equivalent, we generated knock-in mice in which Otx2 was replaced by Otx1. In homozygous mutants, gastrulation occurred normally, and rostral neuroectoderm was induced at 7.5 days postcoitus (7.5 dpc), but the rostral brain failed to develop. Anterior structures such as eyes and the anterior neural ridge were lost by 8.5 dpc, but the isthmus and r1 and r2 were formed. In regionalization of the rostral neuroectoderm, the cooperative interaction of Otx2 with Otx1 revealed by the phenotype of Otx2 and Otx1 double heterozygotes was substitutable by Otx1. The otocephalic phenotype indicative of Otx2 haploinsufficiency was also largely restored by knocked-in Otx1. Thus most Otx2 functions were replaceable by Otx1, but the requirement for Otx2 in the anterior neuroectoderm prior to onset of Otx1 expression was not. These data indicate that Otx2 may have evolved new functions required for establishment of anterior neuroectoderm that Otx1 cannot perform.

Animals↗

PubMed1998

Amyloid beta-protein (A beta) accumulation in the putamen and mammillary body during aging and in Alzheimer disease.

Immunocytochemical studies clearly showed that amyloid beta-protein (A beta) deposits are widely distributed in the subcortical regions as well as the cortices of normal aged and Alzheimer disease (AD) brains. To investigate the temporal profile of A beta accumulation in the subcortical region, we quantitated A beta40 and A beta42 levels, using sensitive enzyme immunoassays, in the putamen and mammillary bodies of normal individuals aged 24 to 87 years and of AD patients. In these two regions, A beta42 was the predominant species; in particular, A beta42 was the only A beta species detected in the putamen. In several cases the mammillary body contained only A beta40, but not A beta42. Although the extent of A beta accumulation in the 2 subcortical regions was much less than that in the cortex of the same subject, A beta42 appears to accumulate in both subcortical regions at the same time as in the cortex and leptomeninges. In addition, the A beta42 levels in the putamen or in the mammillary body correlated with those in the occipitotemporal cortex. This strongly suggests that the extent of A beta42 accumulation in the brain is determined not only by the duration of A beta accumulation but also by other unknown regional factors. Western blotting showed that the initial A beta species to accumulate in the putamen or mammillary body varied among individuals. In some cases, an A beta42 stable dimer was the most predominant species, while in other cases a 3 or 4 kD A beta42 monomer was more abundant, suggesting that the clearance rates of the A beta42 stable dimer and monomer are different in vivo.

Adult↗

PubMed1987

A critical view of presbyopic add determination.

From a previous study at the Optometric Center of Fullerton, it was found that 17.5% of the review clinic population returned due to improper presbyopic reading adds. The population sample for the present study consisted of patients between 40-60 years of age who returned to the clinic between September 1983 and May 1985 due to improper add power. The add power originally prescribed was compared to each of four commonly used methods of add power determination. Our results indicate that the age expected add powers account for the fewest errors while the binocular cross cylinder the most. Upper and lower limits for an acceptable range of add powers versus age were determined.

Age Factors↗

PubMed1982

The lethal protein from Kintoki beans (Phaseolus vulgaris) identified as a lectin.

A glycoprotein isolated from Kintoki beans (Phaseolus vulgaris cultivar Kintoki) agglutinated human erythrocytes of all types and erythrocytes of rat, rabbit, sheep, and mouse. The lectin activity was not affected by 1 hr heating at 60 degrees C, but decreased slightly on heating for the same period at 70-80 degrees C and markedly at 90-100 degrees C. The activity was inhibited by galactose, lactose, N-acetyl galactosamine and fetuin. The inhibition was, however, weak, as often found for nonspecific lectins. The activity did not change when tyrosine residues or small parts of amino groups were modified, but decreased considerably when histidine residues or carboxyl groups were modified. This lectin was found to be relatively resistant to trypsin, and, particularly, to pepsin. All mice died within 48 hr when 200 microgram lectin per gram body weight was injected intraperitoneally and 14 microgram intravenously. The toxic activity changed in parallel with the lectin activity upon various treatments of the glycoprotein. In addition, blood analyses of injected mice suggested that the toxicity might be developed by the action of the lectin on blood cells.

Animals↗