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Biomedical subjects

N Goto

Publications and source records attributed to N Goto.

At least 145 records · Page 8Linked to original sources

A retrospective study of canine senile plaques and cerebral amyloid angiopathy.

Epidemiologic and morphologic features of canine senile plaques (SPs) and cerebral amyloid angiopathy (CAA) were examined in 69 necropsied dogs. Dogs having only SPs (diffuse plaques) frequently suffered from malignant neoplasms, and their mean age was significantly lower than that of dogs with CAA only. Morphologically, diffuse plaques showed wide distribution compared with amyloid plaques or CAA and were predominantly concentrated in the frontal cortex. We were unable to find any significant relationship between the severity of the SPs and individual age. These findings may indicate that the occurrence of canine SPs is not strictly associated with aging only and that additional factors are related to the occurrence of SPs, especially diffuse plaques.

Age Factors↗

Renal glomerular fibrosis in a cat.

Renal glomerular fibrosis was observed in a 1-year-old spayed female Japanese domestic cat that showed clinically advanced renal failure. In the glomeruli, increased homogeneous materials were stained strongly with aniline blue by Masson's trichrome and positive for anti-type III collagen antibody by immunohistochemical staining, causing mesangial sclerosis and capillary collapse. By electron microscopy, randomly arranged fibrils were observed in the expanded subendothelial and mesangial areas, and the fibrils showed periodicity characteristic of collagen fibers in longitudinal sections. These findings of glomerular lesions closely resemble those of human "collagenofibrotic glomerulonephropathy," which has recently been described as a new type of glomerulonephropathy.

Animals↗

[Bayesian forecasting of plasma vancomycin concentration using time-dependent pharmacokinetics].

A new prediction method of vancomycin (VCM) pharmacokinetics has been developed using the modified Bayesian forecasting method involved in time-dependent pharmacokinetics in clearance. We investigated to evaluate the usefulness of this new prediction method compared with that of the ordinary Bayesian forecasting method. Serum samples, obtained from 4 patients at least 3 different days during the period for the VCM treatment were assayed by fluorescence polarization immunoassay. VCM pharmacokinetic parameters and predicted serum VCM concentrations were calculated using this new method and the ordinary one according to the one-compartment model. The precision of the predicted serum VCM concentrations by these two methods at the third experimental day were evaluated with the mean prediction error (ME), mean absolute prediction error (MAE) and root mean squared error (RMSE). The most precise and least-bias prediction of serum VCM concentrations were observed using this new prediction method (ME: -0.36 +/- 1.40, MAE: 1.13 +/- 0.82 and RSME: 1.37). The time-dependent decrease of VCM clearance was observed in all patients. Therefore, the fitting of the actual serum VCM concentrations obtained using the ordinary method produced less precise results than that using this new method. These results suggest the usefulness of this new prediction method considering time-dependent changes in VCM clearance.

Aged↗

Factors affecting induction of neurological disorders in mice by paralysis-inducing Friend-related PVC viruses.

Our previous studies showed that the passage of the Friend virus complex through rats generated variant MuLVs, designated PVC111, PVC211, PVC321 and PVC441, that induced neurological disorders associated with tremor and paralysis. In this study, we tested the pathogenicity of four different PVC viruses in mice. Although histopathological studies revealed spongiform degeneration in the spinal cords of NFS mice infected with each PVC virus, only PVC441 frequently induced tremor and paralysis. After a long latency, all of these viruses induced leukemia associated with severe anemia. Further studies with PVC441 revealed dose- and age-dependence for tremor induction. In contrast to NFS mice, BALB/c, DBA/2 and C57BL/6 mice infected with PVC441 virus showed no neurological symptoms, although the virus could be isolated from the tissues of central nervous system. Despite the absence of neurological symptoms, a high degree of neuronal degeneration in the lumbar spinal cord was found in PVC441-infected BALB/c mice. A low degree of neuronal degeneration was found in PVC441-infected DBA/2 or C57BL/6 mice. Genetic crosses of these resistant mice with susceptible NFS mice indicated that resistance to tremor induction by PVC441 was dominant in all mouse strains and suggested that various host genes may control the susceptibility of mice to tremor induction by PVC441 virus.

Animals↗

Spontaneous vascular mineralization in the brain of horses.

Cerebral vascular mineralization was found in 12 (60%) of 20 3- to 10-year-old healthy horses collected at an abattoir. It was variable in degree and occurred mostly in the pallidal arteries showing two types of lesions; small globoid bodies along capillaries, and amorphous deposits in the wall of arterioles, small- or medium-sized arteries and veins. Both types were strongly positive for periodic acid-Schiff reaction, and weakly positive for von Kossa's and Berlin blue stains. Elemental analysis of the deposit revealed the presence of large amounts of aluminum, moderate amounts of phosphorus, zinc, calcium and iron, and a small amount of sodium.

Aging↗

Hepatitogenicity of three plaque purified variants of hepatotropic mouse hepatitis virus, MHV-2 in athymic nude mice.

Hepatitogenicity of 3 plaque purified variants of hepatotropic mouse hepatitis virus, MHV-2 were examined in athymic BALB/c-nu/nu mice up to 9 weeks post infection (9WPI). All of the MHV-2S- and MHV-2M-infected mice died with severe acute hepatitis in 3WPI. On the other hand, MHV-2L-infected mice did not die until 9WPI and showed signs of slow-developing chronic hepatitis with persistent infection under low serum virus neutralizing antibody titers. This suggests that MHV-2L-infected athymic nude mice may be useful as a new model of chronic viral hepatitis.

Animals↗

Immunohistochemical study on the deposition of apolipoprotein E in cerebral and islet amyloidoses in cynomolgus monkeys (Macaca fascicularis).

To investigate the role of apolipoprotein E (apo E) in amyloidoses of cynomolgus monkeys, the localization of apo E in cerebral amyloid, including senile plaques and cerebrovascular amyloid, and in islet amyloid was examined immunohistochemically. Mature types of senile plaques with amyloid deposits and cerebrovascular amyloid showed intense immunoreactivity to both antisera to apo E and amyloid beta protein (A beta). In contrast, diffuse plaques without obvious Congophilic amyloid showed weak immunoreactivity to antiserum to apo E, but intense reactivity to antiserum to A beta. In addition, the number of these apo E-positive diffuse plaques was small compared with that of A beta-positive plaques. On the other hand, diabetic islet amyloid that was negative with A beta, reacted intensely with antiserum to apo E. These findings suggest that apo E plays an important role in amyloid fibril formation in several types of amyloidoses.

Amyloid↗

Protective effect of recombinant interferon (IFN)-alpha/beta on MHV-2cc-induced chronic hepatitis in athymic nude mice.

The protective effects of recombinant IFN-alpha/beta on MHV-2cc-induced chronic and persistent hepatitis in athymic nude mice were examined. The mice intraperitoneally (ip) inoculated with MHV-2cc at day 0 of experiment were divided into 4 groups. Three of them were administered ip with recombinant IFN-alpha/beta at a daily dose of 1 x 10(3) IU from -1 (-1D-group), 0 (0D-group), and +1 day of experiment (+1D-group), respectively, for 3 consecutive weeks. The remaining one (control group) was given 0.1 ml/mouse of PBS from +1 day of the experiment in the same way. Three mice in each group were killed at 1, 2 and 3 weeks post inoculation (WPI) with MHV, respectively. The liver virus titer in the control group increased gradually and maintained high levels throughout the experimental period. In the IFN-groups, particularly in the -1D- and 0D-groups, the virus titers were significantly lower than that in control group. Histopathologically, focal hepatic lesions were observed at 1WPI and large irregular inflammatory lesions developed at 3WPI in the control group. Similar but somewhat less severe lesions were observed in the +1D-group. In the -1D- and 0D-groups, lesions were not observed at 1WPI and only small organized lesions with mononuclear cell infiltration were seen at 3WPI. In conclusion, it was clarified in the present study that the progression of MHV-2cc-induced chronic hepatitis in athymic nude mice was effectively prevented by extrinsic IFN-alpha/beta when administered from -1 day and 0 day of the virus infection.

Animals↗

Analysis of mandible of newly developing strain of Japanese white rabbit (Nib:JWNS).

In the present paper, we applied analysis of the mandible to a new strain of Japanese White rabbit being developed (Nib: JWNS), at 5th and 8th generations (F5 and F8), and evaluated the process of establishment, making comparison with the parent colonies (I, K and L), and other established JW colonies (A, E, O and R). The mandibles were measured at 12 sites and the data obtained were calculated by principal component analysis and discriminant analysis. As a result of principal component analysis, the parent colonies were found to be close to one another with intermediate size of the mandible and height of condyloid and angular processes, but in F5 and F8 the mandibles were slightly shorter in height and different from those in the parent colonies. On the other hand, results of discriminant analysis revealed that mandibles were discriminated correctly 100% in colonies A, O and R, and 90% in E and I. Colonies A, O, R, E and I were therefore regarded as established strains. In the developing colonies, the discriminant rate was 70% in F5 and 80% in F8. One mandible from F5 and two from F8 were wrongly classified to the parent colony L, which was the lowest discriminant rate among the colonies examined (61.5%). The results of both statistical analyses suggest that the JWNS are almost established at 8th generation as a new strain.

Animals↗

Age-related reductions in number and size of anterior horn cells at C6 level of the human spinal cord.

We examined numbers and sizes of anterior horn cells (AHCs) of the human spinal cord at C6 level with aging process. Spinal cords were obtained from twenty-four male cadavers, age ranged from 41 to 97 years without any accompanying pathological changes of the spinal cord. For quantitative investigation of the AHCs, spinal cord segments were embedded in celloidin after secondary fixation and dehydration; sections (20 microns thick) were stained with luxol fast blue-periodic acid-Schiff-hematoxylin and Klüver-Barrera methods; the neuronal number, the cell body area and the perimeter of AHCs in the gray matter (equivalent to the Rexed's lamina IX) were counted and measured using a combination of a microscope with a drawing tube, a digitizer and a computer at 400 times magnification. A marked reduction in number of AHCs was found in the aged subjects. Similarly, there were significantly age-related decreases in the cross-sectional area and perimeter of AHCs at C6 segment of the spinal cord. These findings indicate that the reduction in number and size of AHCs in the human spinal cord is associated with degenerative neuronal changes and loss of motoneurons during aging process.

Adult↗

Distribution of amyloid bodies in the aged human vestibulocochlear nerve.

We tried to elucidate the localization and distribution of amyloid bodies (Corpora amylacea) in the human vestibulocochlear nerve stained with luxol fast blue-periodic acid Schiff-hematoxylin using of a combination of an image analyzing computer system and a microscope fitted with a drawing tube. After having observed each section of the vestibulocochlear nerve from the brain stem to the fundus of the internal auditory meatus, we counted the numbers of amyloid bodies in three different parts for each of three corpses, and measured the areas. We found that amyloid bodies of the vestibulocochlear nerve are concentrated to the limiting glial portion of the nerve more than to the nerve parenchyma, and amyloid bodies are not seen in the vestibulocochlear nerve peripheral to the transitional zone. Our quantitative trial proved that the amyloid body was larger in the 8th decade than in the 6th or 7th decade of life.

Aged↗

[A new embedding material for morphometry: Shiojirin E-10].

For morphometric studies, sections have been stained with the Luxol fast blue-PAS-Hematoxylin (LPH) staining method after secondary fixation with chromic acid followed by embedding in Celloidin to measure the area of nerve cells or axons with the help of an image analyzer and a microscope. However, the manufacture of Celloidin has been suspended in Japan. Therefore, we studied the use of Shiojirin E-10 (10% nitrocellulose ether alcohol solution) as a substitute embedding material, and compared it with Celloidin from the viewpoint of tissue shrinkage and staining characteristics. Regarding the shrinkage ratio of LPH-stained sections of human cauda equina, there was no practical difference in the axonal areas (p < 0.01) between Celloidin sections (4.31 +/- 2.55 microns2) and Shiojirin E-10 sections (4.14 +/- 2.20 microns2). Regarding staining characteristics, we introduced a hue analysis method using computerized digital signals converted from pictures of stained sections taken by a videocamera. For the evaluation of hue, we examined the H-E sections of mouse liver and kidney, and the LPH sections of the human cauda equina. The hematoxylin hues of the H-E sections were 295 degrees for Celloidin and 294 degrees for Shiojirin E-10. Eosin hues of the E-E sections were 320 degrees for both embedding material. The axonal hues of the LPH stain were 254 degrees for Celloidin and 251 degrees for Shiojirin E-10. Myelin sheath hues were 224 degrees for both embedding material. According to our results, Shiojirin E-10 can be substituted for Celloidin from the qualitative and quantitative viewpoints in the morphologic studies.

Animals↗

Carboxyl end-specific monoclonal antibodies to amyloid beta protein (A beta) subtypes (A beta 40 and A beta 42(43)) differentiate A beta in senile plaques and amyloid angiopathy in brains of aged cynomolgus monkeys.

Senile plaques (SPs) and cerebral amyloid angiopathy (CAA) in the brains of five aged (20-26 years old) cynomolgus monkeys were investigated immunohistochemically using two monoclonal antibodies (anti-A beta 40 (BA27) and anti-A beta 42(43) (BC05)) that can differentiate the carboxyl termini of amyloid beta protein (A beta) subtypes. In four of five animals, all types of SPs (i.e. diffuse, primitive, and classical plaques; DPs, PPs, and CPs, respectively) were identified by BC05. However, BA27 did not label DPs and stained only about one third of PPs and CPs, mainly labeling granular structures and cored portions, respectively. In CAA, lesions of cortical capillaries reacted to BC05 in four of five cases, but rarely and weakly to BA27 in two of five cases. On the other hand, lesions of parenchymal and meningeal arterioles were stained by both BA27 and BC05. These staining profiles of SPs in cynomolgus monkeys correspond well to those in humans, although there are two remarkable features in cynomolgus monkeys. First, BA27 stained PPs associated with granular structures. Secondly, capillary A beta reacted intensely to BC05 but only slightly to BA27. Despite these unique features, the results suggest that aged cynomolgus monkeys can be used to investigate the pathogenesis of A beta deposition in SPs and CAA.

Amyloid beta-Peptides↗

Senile plaques in an aged two-humped (Bactrian) camel (Camelus bactrianus).

Senile plaques with beta-protein as a major constituent are a conspicuous feature in the brains of aged humans, monkeys, dogs, and bears. We found cerebral senile plaques of the diffuse and primitive type, but not the classical type, in an aged female camel of more than 20 years old. The senile plaques and a few cortical capillaries were immunoreactive with anti-beta-protein serum. Congophilic amyloid deposition was detected in a small number of the capillaries, but not in the senile plaques. We believe this to be the first detailed report of senile plaques in a herbivore, and these findings suggest the possibility of senile plaque formation in a wide variety of mammalian species.

Aging↗