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Biomedical subjects

I Sakakibara

Publications and source records attributed to I Sakakibara.

At least 37 records · Page 2Linked to original sources

First isolation of Sarcocystis hominis from cattle in Japan.

Sarcocystis hominis was first isolated from slaughtered cattle raised in Japan. Cysts were 1,220-4,460 x 80-384 microns in size and their wall was 3 to 6 microns thick and appeared radially striated in the histopathological sections because of the presence of palisade-like villar protrusions on the surface. The protrusions were 3.1-4.3 x 0.7-1.1 microns in size and had many microtubules in the core. Two cynomolgus monkeys, Macaca fascicularis, fed with the Sarcocystis cysts began to pass sporocysts, which measured a size of 14.3-15 x 9.5-10 microns, in the feces 10 days after ingestion.

Animals↗

Opportunistic Pneumocystis carinii infection in red-bellied tamarins (Saguinus labiatus).

P. carinii infection in red-bellied tamarins (Saguinus labiatus), born and maintained in a laboratory breeding colony, was examined by histopathologic examination postmortem. P. carinii cysts were detected in 6 of 10 red-bellied tamarins examined, by using Grocott's, toluidine blue O and immunostaining with avidin-biotin complex using antisera for rat-, simian-, and human-P. carinii. The results obtained from the present studies imply that P. carinii may be an important pathogen in this species.

Animals↗

Simian T cell leukemia virus type I-induced malignant adult T cell leukemia-like disease in a naturally infected African green monkey: implication of CD8+ T cell leukemia.

Spontaneous T cell leukemia was found in an African green monkey (Cercopithecus aethiops, AGM) naturally infected with simian T cell leukemia virus type I (STLV-I). The hematological features and the evidence for monoclonal integration of provirus DNA in the leukemic cells revealed that the leukemia was an ATL-like disease. The expression of surface markers on the leukemic cells indicated that they were defined as an activated CD8+ T cell subset. Together with the finding that seven in vitro spontaneously STLV-I-transformed cell lines were CD4-CD8+, it is likely that CD8+ T cells are transformed by STLV-I in AGMs, in contrast with human ATL. Finally, we assessed characteristics of the CD8 chains on these transformed cells. The result indicated that the leukemic cells expressed only the alpha chains but not the beta chains. However, in the case of in vitro-transformed cell lines the expression pattern of the CD8 chains varied in individual monkeys. Thus, STLV-I may preferentially transform CD8+ (both alphaalpha+ and alphabeta+) T cells in AGMs.

Adult↗

Histopathological studies of senile plaques and cerebral amyloidosis in cynomolgus monkeys.

Senile plaques (SPs) and cerebral amyloid angiopathy (CAA), pathological hallmarks of Alzheimer's disease, have not been thoroughly investigated histopathologically in nonhuman primates. To determine the onset age and histopathological characteristics of SPs and CAA, we examined the brains of 64 cynomolgus monkeys (Macaca fascicularis) from 2 to 35 years old. Mature (classical and primitive) plaques appeared in 16 out of 25 monkeys that were >20 years old. Moreover, mature plaques were observed more frequently than diffuse plaques and were located in the temporal cortex of the superior or inferior gyri and amygdala. Diffuse plaques in contrast to mature plaques did not show definite tendencies in onset age and distribution. CAA appeared in more than 22-year-old monkeys in 10 out of 16 animals and was frequently observed in capillaries and often found adjoining mature plaques. During immunohistochemical examination, an antiserum for amyloid beta protein (A beta) 1-40 could detect all SPs, whereas a monoclonal antibody for A beta 8-17 could not detect any diffuse plaques and only one third of the primitive plaques. As for CAA, the polyclonal antiserum was more sensitive than the monoclonal antibody. The present study describes the histopathological features of SPs and CAA in old cynomolgus monkeys.

Aging↗

Baicalin and baicalein, constituents of an important medicinal plant, inhibit intracellular Ca2+ elevation by reducing phospholipase C activity in C6 rat glioma cells.

Glial cells have a role in maintaining the function of neural cells. This study was undertaken to clarify the effects of baicalin and baicalein, flavonoids isolated from an important medicinal plant Scutellariae Radix (the root of Scutellaria baicalensis Georgi), on glial cell function using C6 rat glioma cells. Baicalin and baicalein caused concentration-dependent inhibition of a histamine-induced increase in intracellular Ca2+ concentrations ([Ca2+]i). The potency of baicalein was significantly greater than that of baicalin. The noradrenaline- and carbachol-induced increase in [Ca2+]i was also inhibited by baicalein and both drugs inhibited histamine-induced accumulation of total [3H]inositol phosphates, consistent with their inhibition of the increase in [Ca2+]i. These results suggest that baicalin and baicalein inhibit [Ca2+]i elevation by reducing phospholipase C activity. The inhibitory effects of baicalin and baicalein on [Ca2+]i elevation might be important in the interpretation of their pharmacological action on glial cells, such as inhibition of Ca2(+)-required enzyme phospholipase A2.

Animals↗

Effects of Sho-saiko-to, San'o-shashin-to and Scutellariae Radix on intracellular Ca2+ mobilization in C6 rat glioma cells.

Glial cells are able to support neurons physically and functionally. The present study was undertaken to determine the effects of Kampo medicines on glial cell function, especially Ca2+ mobilization. C6 rat glioma cells expressed H1-histamine, muscarinic cholinergic and adrenergic alpha1-receptors, stimulation of which resulted in phosphoinositide hydrolysis and increase in intracellular Ca2+ concentrations ([Ca2+]i). The water extracts of Sho-saiko-to and San'o-shashin-to, Kampo medicines which contain Scutellariae Radix (Ogon, the root of Scutellaria baicalensis GFORGI), inhibited histamine (100 microM)-induced increase in [Ca2+]i in a concentration-dependent manner. The water extract of Scutellariae Radix potently decreased [Ca2+]i in a concentration-dependent manner. Sho-saiko-to, San'o-shashin-to and Scutellariae Radix significantly inhibited histamine-induced accumulation of total [3H]inositol phosphates, consistent with their inhibition of the increase in [Ca2+1]i. These results suggest that Sho-saiko-to, San'o-shashin-to and Scutellariae Radix inhibit Ca2+ mobilization mediated via an inhibition of phospholipase C. The inhibitory effect may be important in interpreting the pharmacological actions of above Kampo medicines.

Animals↗

Immunohistochemical characteristics of the constituents of senile plaques and amyloid angiopathy in aged cynomolgus monkeys.

In this study, we immunohistochemically examined the several constituents of senile plaques (SPs) and cerebral amyloid angiopathy (CAA) in aged cynomolgus monkeys. Apolipoprotein E (apoE) deposited in all mature plaques and CAA, and in half of the diffuse plaques. Alpha-1-antichymotripsin (alpha ACT) deposited in half of the mature plaques and in one third of the CAA. Amyloid precursor protein (APP), ubiquitin (Ub), and microtubule-associated protein-2 (MAP-2) accumulated in the swollen neurites of mature plaques. Glial fibrillary acidic protein (GFAP) was detected in the astrocytes and their processes surrounding the mature plaques. Tau was detected in neither the SPs nor CAA. Therefore, mature plaques involved extracellular A beta, apoE, and alpha ACT, and also astrocytes and swollen neurites. However, diffuse plaques involved only extracellular A beta and apoE. Since these features, except for tau, were consistent with those in humans, this animal model will be useful for studying the pathogenesis of cerebral amyloid deposition.

Aging↗

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↗

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↗

[Histopathological studies on senile plaques and cerebral amyloid angiopathy in aged cynomolgus monkeys].

The incidence and morphological characteristics of senile plaque and amyloid angiopathy in the cerebrum of six aged cynomolgus monkeys (Macaca fascicularis), 20 to 29 years old, were studied histopathologically and immunohistochemically. By periodic acid methenamine silver stain (PAM) and alkaline Congo red stain, senile plaques were detected in 5 out of 6 cases, and 3 of them were positive for amyloid in the wall of capillaries and arterioles in the cerebral cortex. Senile plaques were classified into three types. Mature plaques, including classical and primitive types, were more frequently observed than the immature diffuse type. Senile plaques were often seen in the cortex of temporal lobe, putamen and head of caudate nucleus. Since mature types of senile plaques were seen frequently around vascular amyloid deposition and no amyloid angiopathy was detected in the areas without senile plaques, the close relation between senile plaque of the mature type and amyloid angiopathy might be considered. All senile plaques and amyloid angiopathy were positively stained immunohistochemically with antibody against amyloid beta-protein (A beta P) 1-40 synthetic peptide, but all diffuse and some primitive plaques were negative for antibody against A beta P 8-17 synthetic peptide. Neither senile plaque nor amyloid angiopathy was detected in the cerebrum of 15 young monkeys, 9 to 11 years old, examined as controls.

Aging↗

Severe pulmonary pneumocystosis in simian acquired immunodeficiency syndrome induced by simian immunodeficiency virus: its characterization by the polymerase-chain-reaction method and failure of experimental transmission to immunodeficient animals.

Pneumocystis carinii (Pc) infection was observed in three of five rhesus monkeys infected with simian immunodeficiency virus (SIVmac251). They showed severe symptoms similar to those associated with human acquired immunodeficiency syndrome (AIDS). Histopathology revealed severe pulmonary pneumocystosis in one of three Pc-positive monkeys, and anti-Pc antibodies were detected in sera from two of the three monkeys. Localization of Pc organisms in various organs of the monkeys was examined by the polymerase-chain-reaction (PCR) method, and Pc-specific bands of DNA amplification were detected in the liver, kidney, spleen, adrenal gland, testis, brain, and other organs examined, but no Pc organism was found in these organs by histopathologic examination. These results suggest that the activation of a latent infection of Pc occurs in SIV-infected rhesus monkeys as well as in human AIDS. Experimental transmission of Pc derived from a simian was attempted in severe combined immunodeficiency (SCID) mice and athymic nude (rnu/rnu, F344) rats. These animals were inoculated intranasally with 10(4) Pc cysts, but neither histopathologic changes nor Pc organisms were detected in SCID mice at 4 months after inoculation or in nude rats at 2 months postinoculation, suggesting that simian Pc is species-specific.

Animals↗

Experimental infection of African green monkeys and cynomolgus monkeys with a SIVAGM strain isolated from a healthy African green monkey.

An infection occurred in all African green monkeys and cynomolgus monkeys experimentally inoculated with SIVAGM [TYO-1], as demonstrated by the appearance of an antibody to SIVAGM [TYO-1] and the isolation of the virus. No monkey exhibited overt clinical disorders throughout the experimental period of 42 weeks. Thus, SIVAGM was not pathogenic to its original host or to macaques. This system is proposed as a model for HIV infection manifesting no overt disease.

Animals↗

An outbreak of salmonellosis in newly imported cynomolgus monkeys.

Serious salmonellosis occurred in groups of cynomolgus monkeys newly imported into Tsukuba Primate Center for Medical Science from the Philippines in 1985. During the quarantine period, Salmonella typhimurium (29 strains) and S. stanley (1 strain) were isolated from 30 of 130 imported monkeys. Twenty-eight of the 30 infected monkeys excreted mainly watery diarrhea, and occasionally bloody mucous stool. Seven of the 28 clinical cases infected with S. typhimurium resulted in death or in moribund state. In both the small and large intestines of autopsied monkeys, acute inflammatory changes were observed.

Agglutinins↗