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Biomedical subjects

K Itoh

Publications and source records attributed to K Itoh.

At least 19 recordsLinked to original sources
PubMed1992

[Abnormal chest shadow on CT in immunosuppressed patients].

An abnormal chest shadow was observed on CT scans in 25 cases of 23 immunosuppressed patients. Pulmonary disease was pathologically confirmed to be pneumocystis carinii pneumonia (PC pneumonia) in four patients, cytomegalovirus pneumonia (CMV pneumonia) in one, bacterial pneumonia in seven, fungal infection in three, miliary tuberculosis in one, leukemic infiltration in two, lymphangitis carcinomatosa in three, drug-induced pneumonitis in three, and ARDS in one. In almost all patients, especially those with infectious diseases such as PC pneumonia, CMV pneumonia, and bacterial pneumonia, the abnormal shadow was wide and visible in the bilateral lung fields. We presumed that such findings as lobular shadow, centrilobular shadow, and mosaic pattern reflected the extension of disease via the respiratory tract, and that those findings are typical of infectious diseases. Because such findings as abnormal linear shadow and swelling of a broncho-vascular bundle were very frequently recognized in patients with lymphangitis carcinomatosa and frequently recognized in those with drug-induced pneumonitis, these diseases may be distinguished from other diseases. An area of slightly increased density was frequently recognized in patients with PC pneumonia, bacterial pneumonia, and drug-induced pneumonitis. Such lesions were pathologically confirmed to be located in the interstitium and/or alveolus. CT was extremely useful in comprehending the character and extension of particular diseases among various diseases. As the number of patients studied was small, the utility of CT in immunosuppressed patients requires further investigation in a larger number of patients.

Adolescent↗
PubMed1992

Interleukin-2 (IL-2) induces erythroid differentiation and tyrosine phosphorylation in ELM-I-1 cells transfected with a human IL-2 receptor beta chain cDNA.

The molecular mechanism of erythroid differentiation has been still ill-defined. In this study, we introduced a human interleukin-2 receptor (IL-2R) beta chain cDNA into ELM-I-1 cells which differentiated into hemoglobin-positive cells in the presence of erythropoietin (Epo), and established the transformant which expressed IL-2R beta chain. In this transformant, we revealed that IL-2 induced erythroid differentiation and the same pattern of tyrosine phosphorylation as Epo. These data suggest that tyrosine phosphorylation is involved in signal transduction pathway of erythroid differentiation. It is also implicated that the Epo and IL-2 receptor system share a common signal transduction pathway.

Animals↗
PubMed1992

Genetically engineered rice resistant to rice stripe virus, an insect-transmitted virus.

The coat protein (CP) gene of rice stripe virus was introduced into two japonica varieties of rice by electroporation of protoplasts. The resultant transgenic plants expressed the CP at high levels (up to 0.5% of total soluble protein) and exhibited a significant level of resistance to virus infection. Plants derived from selfed progeny of the primary transformants also expressed the CP and showed viral resistance, indicating stable transmission of the CP gene and the trait of resistance to the next generation. Moreover, the virally encoded strip disease-specific protein was not detected in transgenic plants expressing CP 8 weeks after inoculation, indicating protection before viral multiplication. These studies demonstrated that CP-mediated resistance to virus infection can be extended to cereals and to the viruses transmitted by an insect vector (planthopper).

Base Sequence↗
PubMed1992

Cell adhesion molecule L1 guides cell migration in primary reaggregation cultures of mouse cerebellar cells.

We demonstrate a new assay in vitro using reaggregated cerebellar neurons in order to test the role of the L1 molecule in migration events. Cells other than neurons were eliminated in these cultures. Cerebellar neuron reaggregates plated on L1 molecule substrates migrated at rates similar to those observed in vivo. This migration was blocked by anti-L1 antibody. These findings suggest that this culture could provide a useful system with which to directly study relationships between neuron migration and adhesion molecules.

Animals↗
PubMed1992

Distribution of autologous tumor-specific cytotoxic T lymphocytes in human metastatic melanoma.

The study of specific immunity in human cancers has been hampered by the elusive distribution and heterogeneity of effector cells. In this study, we have investigated the distribution of autologous melanoma-specific cytotoxic T lymphocytes (CTLs) in 18 different distant metastases from melanomas (9 non-visceral and 9 visceral metastases). Uncultured cells from tumors were provided directly for the establishment of T-cell clones using limiting dilution analysis to avoid any possible effects of in vitro sensitization of T cells to coexisting tumor cells. Autologous tumor specific CTL clones were detected in 6 of 18 tumors (33%, 4 non-visceral and 2 visceral metastases). The majority of CTL clones (35 of 46 and 17 of 19) in 2 patients with HLA class-I A2 haplotype failed to lyse either A2+ or A2- allogeneic melanoma cells, although anti-class-I (monomorphic) MAb inhibited their cytotoxicity. The remaining 11 of 46 and 2 of 19 CTL clones showed A2-restricted cytotoxicity. Autologous tumor-specific cytotoxicity was also detected after polyclonal culture of these tumor-infiltrating lymphocytes (TILs) in 8 of 16 tumors (50%, 5 non-visceral and 3 visceral metastases). These results suggest that tumor-specific T cells exist at tumor sites in at least one-third of distant metastases of melanomas and could be induced by the addition of IL-2 in at least half of the tumors. Tumor-specific T cells were detectable more often in non-visceral than in visceral metastases.

Antibodies, Monoclonal↗
PubMed1992

Diphosphorylation of platelet myosin ex vivo in the initial phase of activation by thrombin.

We prepared anti-platelet 20-kDa myosin light chain (MLC-20) antibody and demonstrated diphosphorylation of MLC-20 in platelets ex vivo in the initial phase of activation by thrombin. Our results are as follows. (1) By Western blotting, using anti-MLC-20 antibody, both mono- and diphosphorylated myosin were seen in the initial phase of aggregation of platelets by thrombin. The peak of the diphosphorylation was later than that of monophosphorylation and the degree of both mono- and diphosphorylation reduced in the process of aggregation. (2) ML-7 (a synthetic inhibitor of MLCK) inhibited both mono- and diphosphorylation of myosin and also blocked aggregation of thrombin-activated platelets. However, H-7 (an inhibitor of protein kinase C) had little effect on either the (di)phosphorylation of myosin or the aggregation of thrombin-activated platelets. (3) Arg-Gly-Asp-Ser (RGDS) peptide, a synthetic anti-adhesive peptide, inhibited aggregation of thrombin-activated platelets in a dose-dependent manner (100-200 microM). However, it had little effect on either mono- or diphosphorylation of myosin in the process of the platelet aggregation stimulated by thrombin. From these results, we conclude that mono- and diphosphorylation of myosin by MLCK play a role in the initial phase of activation of thrombin-stimulated platelets in vivo and that mono- and diphosphorylation of myosin by MLCK precedes the secondary signal mediated by GPIIb/IIIa.

Azepines↗
PubMed1992

[Role of growth hormone in the pathogenesis of dawn phenomenon in IDDM].

The early morning hyperglycemia of diabetic patients has been commonly referred to as the "dawn phenomenon". Recently the nocturnal surges of growth hormone (GH) have been suggested as an important factor in the pathogenesis of the dawn phenomenon. In order to reassess the role of the nocturnal GH secretion in the dawn phenomenon, seven C-peptide negative diabetic patients were studied during 48hr-feedback control using a closed-loop insulin infusion device (Biostator). They received oral sleeping medication only on the first night (control) and sleeping medication with anticholinergic agent (pirenzepine 75mg) on the second night, and blood glucose, insulin requirements, GH and cortisol concentrations during 0000hr and 0700hr were measured. The peak of sleep-induced GH secretions was markedly suppressed by pirenzepine in comparison with the control night (19.8 +/- 3.7 vs. 3.0 +/- 1.2ng/ml; p less than 0.05). Insulin requirements during 0500hr and 0700hr were suppressed significantly by pirenzepine (3.0 +/- 0.2 vs. 2.0 +/- 0.2U/2hr; p less than 0.05). Insulin infusion ratio, i.e. insulin requirements during 0500hr and 0700hr divided by those during 0000hr and 0200hr, was decreased by pirenzepine (2.2 +/- 0.3 vs. 1.5 +/- 0.2; p less than 0.05). There were no significant differences in blood glucose and cortisol concentrations whether or not the anticholinergic agent was given. In conclusion, these results have shown that an anticholinergic agent may be useful in the management of insulin-treated patients with marked dawn phenomenon.

Adult↗
PubMed1992

A novel monoclonal antibody against carbohydrates of L1 cell adhesion molecule causes an influx of calcium in cultured cortical neurons.

We have studied the function of carbohydrates of the L1 molecule, a member of the immunoglobulin superfamily of adhesion molecules, using a novel monoclonal antibody, mAb-L1(2E12), against L1 molecule. This antibody was specific for the 200 kDa component of mouse L1 molecule and its epitope was N-linked for complex-type oligosaccharides. The mAb-L1(2E12) was found to induce a rise in intracellular Ca2+ concentration ([Ca2+]i) in cultured mouse embryonic cortical neurons. The rise in [Ca2+]i was dependent on the concentrations of mAb-L1(2E12). The rise seemed to be due to an influx of extracellular Ca2+ as EGTA treatment abolished it. Both cadmium and nifedipine blocked the effect of mAb-L1(2E12), suggesting the Ca2+ influx was through voltage-operated Ca2+ channels, particularly L-type Ca2+ channels. These results provide an important insight for understanding the mechanisms by which oligosaccharides of the L1 molecule influence various functions of neural cells.

Animals↗
PubMed1992

Human renal-cell carcinoma cells are able to activate natural killer cells.

We previously reported that natural killer (NK) cells that had infiltrated renal-cell carcinoma (RCC) proliferated vigorously in culture with interleukin-2 (IL-2) and lysed autologous tumor cells. In this study, we investigate the susceptibility of RCC cells to NK-cell lysis and their ability to stimulate proliferation and increase phenotypic expression and function of NK cells. Cells from primary culture of RCC (p-RCC cells) were significantly more susceptible to the lysis mediated by human NK3.3 clones than were cells from primary culture of metastatic melanomas. Both RCC-cell clones and cells from primary culture of non-tumorous kidneys were also susceptible to lysis by NK3.3 clones and IL-2-activated peripheral blood lymphocytes (PBLs). Incubation of NK3.3 clones with p-RCC cells in the absence of IL-2 induced proliferation of NK3.3 clones, whereas incubation with cells from primary culture of metastatic melanomas, K562 cells, or any others tested did not. The p-RCC cells from earlier passages were more potent inducers of NK-cell proliferation than were those from older passages. Cell-free culture supernatants of p-RCC cells with or without NK3.3 clones failed to induce NK-cell proliferation. Incubation of CD16+ NK cells purified from PBLs with p-RCC cells induced higher proliferation of the NK cells only in the presence of IL-2, whereas incubation with cells from primary culture of metastatic melanomas did not. Incubation of NK3.3 clones with p-RCC cells resulted in an increase in CD16, CD25 (IL-2 receptor-alpha), and HLA-DR antigen expression and cytotoxicity in NK3.3 clones. In summary, these results suggest that RCC cells are able to activate NK cells, potentially through cell-to-cell interaction.

Antigens, Differentiation↗
PubMed1992

[MR imaging of hilar cholangiocarcinoma--comparative study with CT].

Magnetic resonance (MR) images of 18 cases of hilar cholangiocarcinoma were evaluated to compare the effectiveness of Gd-DTPA with that of high dose contrast enhancement computed tomography (HCE-CT) in detecting the primary tumor. The primary tumor was demonstrated as having slightly low intensity compared with liver parenchyma and high intensity compared with the dilated bile duct on T1 weighted images. In contrast, MRI using Gd-DTPA, which was carried out in five cases, revealed intense enhancement of the tumor. As the differentiation between cholangiocarcinoma and dilated bile duct was difficult, it was concluded that the use of Gd-DTPA improves the efficacy of MRI in diagnosing cholangiocarcinoma. Gd-DTPA was also effective in differentiating the growth pattern of the tumor: the infiltrating type was demonstrated as thickening of the wall of the bile duct, the polypoid type as a soft tissue mass in the bile duct. Contrast MRI study is effective for the detection of cholangiocarcinoma. It is also expected to be effective in the staging diagnosis of cholangiocarcinoma.

Adenoma, Bile Duct↗
PubMed1992

Relationship of urinary pseudouridine and 1-methyladenosine to activity of leukemia and lymphoma.

Urinary levels of pseudouridine and 1-methyladenosine in patients with leukemia and lymphoma were measured by the inhibition ELISA using monoclonal antibodies to determine the correlation of nucleosides excretion with disease activity. Significantly elevated levels of these nucleosides were detected in patients with all types of disease tested. Seventy-seven percent (46/60) and 62% (37/62) of patients had elevated levels of pseudouridine and 1-methyladenosine above normal mean + 2S.D., respectively, and combination assay of these nucleosides gave higher positive rate (87%; 52/60) than either single assay. The changes of urinary pseudouridine and 1-methyladenosine reflected the disease status of patients in remission or in relapse and the effect of chemotherapy. These results suggest that urinary pseudouridine and 1-methyladenosine might be clinically useful as complementary markers to the monitoring of the disease status of patients with leukemia and lymphoma by hematological examination.

Adenosine↗
PubMed1992

[Evaluation of breath-hold multislice dynamic MRI of hepatocellular carcinomas].

The breath-hold multislice dynamic study (BMDS) in MRI, which can scan the entire liver during a single breath-holding, was applied to 16 patients with 30 focal lesions of hepatocellular carcinoma (HCC). The BMDS was performed at 20 seconds and 3 minutes after the bolus injection of Gd-DTPA, by gradient echo pulse sequence (FLASH). 29 nodules were detected in the BMDS, showing rapid enhancement on early phase and decline on delayed phase images. The BMDS was more sensitive than conventional MR images. Therefore, the BMDS seems to be useful for the diagnosis of HCC with multiple as well as solitary nodules.

Carcinoma, Hepatocellular↗
PubMed1992

Diphosphorylation of platelet myosin by myosin light chain kinase.

Recently, one of the authors (K.I.) and other investigators reported that myosin light chain (MLC) of smooth muscle (gizzard, arterial and tracheal) was diphosphorylated by myosin light chain kinase (MLCK) and that diphosphorylated myosin showed a marked increase in the actin-activated myosin ATPase activity in vitro and ex vivo. In this study, we prepared myosin, actin, tropomyosin (human platelet), MLCK (chicken gizzard) and calmodulin (bovine brain) and demonstrated diphosphorylation of MLC of platelet by MLCK in vitro. Our results are as follows. (1) Platelet MLC was diphosphorylated by a relatively high concentration (greater than 20 micrograms/ml) of MLCK in vitro. As a result of diphosphorylation, the actin-activated myosin ATPase activity was increased 3 to 4-fold as compared to the monophosphorylation. (2) Both di- and monophosphorylation reactions showed similar Ca2+, KCl, MgCl2-dependence. Maximal reaction was seen at [Ca2+] greater than 10(-6) M, 60 mM KCl and 2 mM MgCl2. This condition was physiological in activated platelets. (3) Di- and monophosphorylated myosin showed similar Ca2+, KCl-dependence of ATPase activity but distinct MgCl2-dependence. Diphosphorylated myosin showed maximal ATPase activity at 2 mM MgCl2 and monophosphorylated myosin showed a maximum at 10 mM MgCl2. (4) The addition of tropomyosin stimulated actin-activated ATPase activity in both di- and monophosphorylated myosin to the same degree. (5) ML-9, a relatively specific inhibitor of MLCK, inhibited the aggregation of human platelets induced by thrombin ex vivo in a dose-dependent manner. Moreover, this drug also partially inhibited both di- and monophosphorylation reactions and actin-activated ATPase activity. On the other hand, H-7, a synthetic inhibitor of protein kinase C, had little effect on the aggregation of human platelets induced by thrombin ex vivo. From these results, we conclude that diphosphorylation of platelet myosin by MLCK may play an important role in activated platelets in vivo.

Actins↗
PubMed1992

[Detection of intrahepatic lipids by 1H-MRS--studies by breath-holding & 1 cm3 VOI].

The authors performed 1H-MR spectroscopy (MRS) to depict lipids in the liver of 10 healthy volunteers. Spectra were obtained by a 1.5 T-MR unit, with STEAM from 1 x 1 x 1 cm3 VOI. Lipid peaks were depicted in 7 of the 10 volunteers by breath-holding 1H-MRS study, while in only 4 on normal breathing. The existence of lipids could not be depicted through chemical shift imaging adopting in-phase & opposed images. This suggests a clinical utility of 1H-MRS, particularly through breath-holding studies, in depicting lipids from 1 x 1 x 1 cm3 VOI in the liver in vivo.

Humans↗
PubMed1992

Immunophenotype and DNA content of myeloma cells in primary plasma cell leukemia.

To clarify the biological characteristics of the myeloma cells in primary plasma cell leukemia (PCL), we studied the immunological phenotype and DNA content of cells from five patients with primary PCL as compared to those from the patients with typical multiple myeloma (MM). In two of five patients with PCL myeloma cells had B-cell-associated antigens (B1, J5) and surface immunoglobulin in addition to plasma cell associated antigens, suggesting that these cells are immunologically immature as compared to mature plasma cells. Concerning the DNA content of myeloma cells, two of four patients had hypodiploid while two had diploid myeloma cells. In contrast, 24 of the 37 (65%) patients with typical MM had hyperdiploid and 1 had hypodiploid myeloma cells. These observations suggest that the myeloma cells in PCL are immunologically heterogeneous. The increased incidence of hypodiploidy in PCL may explain its relatively poor prognosis as previously shown in those with typical MM and hypodiploid DNA content.

Adult↗
PubMed1992

Gamma/delta T cell antigen receptors expressed on tumor-infiltrating lymphocytes from patients with solid tumors.

The expression of gamma/delta T cell antigen receptors (TcR) in T cell lines or clones derived from tumor-infiltrating lymphocytes (TIL) from patients with solid tumors was investigated. gamma/delta TcR T cell lines were derived from TIL from patients with Wilms tumor, sarcoma or metastatic melanoma by stimulation with autologous tumor cells alone and recombinant interleukin 2 and they exhibited nonspecific cytotoxicity against autologous and allogeneic tumor cells, or cells of the K562 or the MEL21 tumor cell lines. Two T cell lines were derived from a patient with Wilms tumor. One of them expressed a non-disulfide-linked gamma/delta TcR using the 60-kDa gamma chain, whereas, the other expressed a disulfide-linked gamma/delta TcR. A T cell line was derived from a patient with sarcoma and expressed a disulfide-linked gamma/delta TcR, whereas, a T cell line derived from a patient with melanoma expressed a non-disulfide-linked gamma chain of 62 kDa. Several T cell clones were developed from patients with metastatic melanoma or Wilms tumor and expressed either disulfide- or non-disulfide-linked gamma/delta TcR. Northern analysis of RNA from certain of these clones revealed a full-length gamma chain transcript, whereas, the alpha or beta chain transcripts were either absent or truncated. These T cell clones exhibited nonspecific cytotoxicity. Both disulfide- and non-disulfide-linked TIL T cell lines and clones expressed the delta TCS1 determinant. gamma/delta TcR+ cells in freshly prepared TIL from these patients were present in low proportions (less than 5%) and their delta TCS1/delta 1 ratios were within the range observed in the peripheral blood of normal donors. These results demonstrate that both disulfide- and non-disulfide-linked gamma/delta TcR are expressed on T cell lines and clones derived from TIL from solid tumors. Non-disulfide-linked gamma/delta TcR using the 56-66-kDa gamma chain are frequently found on TIL-derived T cell lines and clones. These 56-66-kDa gamma chains are rarely expressed on T cell lines or clones derived from peripheral blood lymphocytes of normal donors.

Cell Line↗
PubMed1992

Specificity of a tumor marker (CA54/61) and its individual epitopes recognized by monoclonal antibodies, MA54 and MA61, in human tumor patients.

The specificity of a tumor marker (CA54/61) and its individual epitopes (CA54 and CA61) recognized by monoclonal antibodies (MA54 and MA61) and expressed by the same tumor marker were studied. Serum levels of CA54 and CA61 were compared with that of CA54/61. In lung adenocarcinoma and ovarian carcinoma, the positive rates of CA61 (42% and 68%) were higher than those of CA54 (32% and 32%) and similar to those of CA54/61 (45% and 74%). The serum levels of CA54 and CA61 showed a significant correlation (r = 0.78), but 22% of tested sera were positive for CA54 and negative for CA61 or negative for CA54 and positive for CA61. It was demonstrated that the tumor specificity between CA54 and CA61 was not same and that the tumor specificity of CA54/61 was similar to that of CA61 rather than CA54. Moreover, the difference in the tumor specificity between CA54 and CA61 was considered to be reflected in the difference in their epitope structure.

Antibodies, Monoclonal↗