Biomedical subjects

E Kanda

Publications and source records attributed to E Kanda.

8 recordsLinked to original sources

PubMed2001

Rac is activated by tumor necrosis factor alpha and is involved in activation of Erk.

Tumor necrosis factor alpha (TNFalpha) activates various signal transduction pathways including those involving phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinases (Erk), c-Jun N-terminal protein kinases (JNK), and p38 kinases. Using the Rac binding domain of PAK (PAK-RBD) as an activation-specific probe, here we demonstrate that TNFalpha very rapidly and transiently activates the Rho family GTPase Rac in L929 cells. The PI3K inhibitor LY294002 significantly inhibited TNFalpha activation of Rac as well as Erk and abolished that of the PI3K target Akt, without showing any inhibitory effects on JNK and p38 activation. Furthermore, TNFalpha activation of Erk was abolished by a dominant negative Rac mutant, Rac17N, or by an activated Rac mutant, Rac12V. These findings suggest that Rac is activated by a mechanism that is at least partly dependent on PI3K in TNFalpha stimulated cells and plays a critical role in activation of the Erk signaling pathway.

Animals↗

PubMed2001

CrkL is recruited through its SH2 domain to the erythropoietin receptor and plays a role in Lyn-mediated receptor signaling.

The erythropoietin (Epo) receptor transduces its signals by activating physically associated tyrosine kinases, mainly Jak2 and Lyn, and thereby inducing tyrosine phosphorylation of various substrates including the Epo receptor (EpoR) itself. We previously demonstrated that, in Epo-stimulated cells, an adapter protein, CrkL, becomes tyrosine-phosphorylated, physically associates with Shc, SHP-2, and Cbl, and plays a role in activation of the Ras/Erk signaling pathway. Here, we demonstrate that Epo induces binding of CrkL to the tyrosine-phosphorylated EpoR and SHIP1 in 32D/EpoR-Wt cells overexpressing CrkL. In vitro binding studies showed that the CrkL SH2 domain directly mediates the EpoR binding, which was specifically inhibited by a synthetic phosphopeptide corresponding to the amino acid sequences at Tyr(460) in the cytoplasmic domain of EpoR. The CrkL SH2 domain was also required for tyrosine phosphorylation of CrkL in Epo-stimulated cells. Overexpression of Lyn induced constitutive phosphorylation of CrkL and activation of Erk, whereas that of a Lyn mutant lacking the tyrosine kinase domain attenuated the Epo-induced phosphorylation of CrkL and activation of Erk. Furthermore, Lyn, but not Jak2, phosphorylated CrkL on tyrosine in in vitro kinase assays. Together, the present study suggests that, upon Epo stimulation, CrkL is recruited to the EpoR through interaction between the CrkL SH2 domain and phosphorylated Tyr(460) in the EpoR cytoplasmic domain and undergoes tyrosine phosphorylation by receptor-associated Lyn to activate the downstream signaling pathway leading to the activation of Erk and Elk-1.

Adaptor Proteins, Signal Transducing↗

PubMed2001

IgA nephropathy with complement deficiency.

We treated a female patient suffering from immunoglobulin A (IgA) nephropathy and congenital deficiency of the ninth component of the complement system (C9). She was admitted with hematuria and proteinuria, and the C9 deficiency was diagnosed based on the low hemolytic activity of 50 % of the hemolytic unit of the complements (CH50) and the normal C3 level in the plasma. Renal biopsy revealed mild mesangial proliferation, and immunofluorescence examination revealed mild mesangial deposits of IgA and C3 with the same distribution. We discuss the pathogenesis of IgA nephropathy and the role of the complements in its progression.

Adult↗

PubMed2000

Rap1 is activated by erythropoietin or interleukin-3 and is involved in regulation of beta1 integrin-mediated hematopoietic cell adhesion.

The CrkL adaptor protein is involved in signaling from the receptor for erythropoietin (Epo) as well as interleukin (IL)-3 and activates beta(1) integrin-mediated hematopoietic cell adhesion through its interaction with C3G, a guanine nucleotide exchange factor for Rap1. We demonstrate here that Epo as well as IL-3 activates Rap1 in an IL-3-dependent hematopoietic cell line, 32D, expressing the Epo receptor. The cytokine-induced activation of Rap1 was augmented in cells that inducibly overexpress CrkL or C3G. The CrkL-mediated enhancement of cell adhesion was inhibited by expression of a dominant negative mutant of Rap1, Rap1A-17N, whereas an activated mutant of Rap1, Rap1A-63E, activated beta(1) integrin-dependent adhesion of hematopoietic cells. In 32D cells, Rap1 was also activated by phorbol 12-myristate 13-acetate and ionomycin, which also enhanced cell adhesion to fibronectin, whereas, an inhibitor of phospholipase C, inhibited both cytokine-induced activation of Rap1 and cell adhesion. It was also demonstrated that Rap1 as well as CrkL is involved in signaling from the EpoR endogenously expressed in a human leukemic cell line, UT-7. These results suggest that Epo and IL-3 activate Rap1 at least partly through the CrkL-C3G complex as well as through additional pathways most likely involving phospholipase Cgamma and strongly implicate Rap1 in regulation of beta(1) integrin-mediated hematopoietic cell adhesion.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Prevalence of dirofilarial infection in raccoon dogs in Japan.

The raccoon dog (Nyctereutes procyonoides viverrinus) is known to acquire canine heartworm (Dirofilaria immitis) infection. We surveyed the prevalence of heartworm infection in free-ranging raccoon dogs in the Nishi-Tama (Tokyo) and Kanagawa areas of Japan. A total of 75 raccoon dog carcasses, including 29 animals from the Nishi-Tama area and 46 from the Kanagawa area, were necropsied between 1992 and 1993. Eight out of 75 raccoon dogs were found to be infected (overall 10.7%). The prevalence of infection was 6 and 16% in Nishi-Tama and Kanagawa, respectively. Microfilarial production was observed in the uterus of one female adult dog.

Animals↗

PubMed2000

[Occurrence of alveolar hydatid disease (multilocular echinococcosis) outside of Hokkaido and a proposal for its prevention].

Alveolar hydatid disease (AHD), had been endemic only in Rebun Island prior to 1945, it is now prevalent throughout the mainland Hokkaido. AHD cases have been reported also in 21 prefectures outside of Hokkaido, e.g. Aomori, Tokyo, Miyagi, etc. Case reports of AHD (n = 135) were reviewed and 76 cases were identified in 21 prefectures outside of Hokkaido in 1926-96. These cases were classified in 4 groups: 1) cases supposedly infected where they lived (n = 19), 2) cases that were infected in Hokkaido (n = 23), 3) cases that were infected in foreign countries (n = 30), 4) cases infected in unidentified places (n = 4). Prefectural distribution and sex ratios were characteristic according to the groups. The first group was supposedly infected were they lived, but it was suggested that this group had some relationship with the epidemics of AHD in Hokkaido. Cases of the 1st and 2nd group were estimated to have been infected prior to early 1970, and it was suggested that these 2 groups will increase the number hereafter in the prefectures outside of Hokkaido because the number of AHD cases has been increasing in the mainland Hokkaido since late 1980.

Adult↗

PubMed1995

Diabetes mellitus carrying a mutation in the mitochondrial tRNA(Leu(UUR)) gene.

We screened 214 Japanese NIDDM (non-insulin-dependent) diabetic patients with a family history of diabetes for mutations in the mitochondrial tRNA(Leu(UUR)) gene using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Six patients were identified as having an A to G transition at position 3243 (3243 mutation), but no patients were detected with a T to C transition at position 3271, in the mitochondrial tRNA(Leu(UUR)) gene. These two mutations were not present in 85 healthy control subjects. It was disclosed that the patients' mothers were also affected by diabetes mellitus in five of the six cases. In these six affected patients, the 3243 mutation shows variable phenotypes, such as the degree of multiple organ involvement, intrafamilial and interfamilial differences in disease characteristics, and the degree of the involvement of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) phenotype. Endocrinological examinations revealed that those diabetic patients with the 3243 mutation show not only beta-cell dysfunction, but also a defect in alpha-cell function, which is considered characteristic of diabetes with the 3243 mutation. When compared with 50 selected diabetic control subjects without the 3243 mutation, whose mothers, but not fathers, were found to have diabetes, it was established statistically that those with the 3243 mutation possess the following clinical characteristics; 1) the age of diabetes onset is lower, 2) they have lean body constitutions, and 3) they are more likely to be treated with insulin than control subjects. We suggest that diabetes with the 3243 mutation possesses phenotypes distinct from those in common forms of diabetes.

Adolescent↗

PubMed1993

Pathology and epidemiology of canine distemper in raccoon dogs (Nyctereutes procyonoides).

From September to December 1991, a large number of free-ranging raccoon dogs (Nyctereutes procyonoides) died from a highly contagious disease in the vicinity of Tokyo. Eighteen seriously ill or dead animals were submitted for necropsy. The pathological findings resembled those in a masked palm civet (Paguma larvata) found infected with canine distemper virus (CDV) in the same area in late August 1991. The most striking features were pneumonia and gastroenteritis. Microscopical lesions consisted of cytoplasmic and intranuclear eosinophilic inclusion bodies in various organs and tissues, bronchiolointerstitial pneumonia, non-suppurative demyelinating encephalitis, lymphocytic depletion in various lymphoid tissues and catarrhal or necrotizing gastroenteritis. CDV-specific antigens, demonstrated immunohistochemically in the epithelial tissues, central nervous system and lymphoid tissues, corresponded with the presence of the eosinophilic inclusion bodies in sections of the same lesions stained with haematoxylin and eosin. Ultrastructurally, both cytoplasmic and intranuclear inclusion bodies were observed to be composed of aggregates of viral nucleocapsids. The study provided clear evidence that CDV was the cause of the disease. It is possible that the masked palm civet introduced the infection into the raccoon dog population.

Acute Disease↗