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Biomedical subjects

H Ito

Publications and source records attributed to H Ito.

At least 19 recordsLinked to original sources

Visual and infrared input to the same dendrite in the tectum opticum of the python, Python regius: electron-microscopic evidence.

In snakes with infrared receptors, the optic tectum receives input from both the visual and the infrared senses. We investigated the infrared and optic fiber terminations in the tectum with a combination of horseradish peroxidase and degeneration labeling. In addition to synapses by visual and infrared fibers onto individual neurons, we were able to observe for the first time visual and infrared synapses on one and the same dendrite.

Animals

Frequent amplification of the c-met gene in scirrhous type stomach cancer.

Amplification of the c-met gene, that encodes hepatocyte growth factor receptor, was examined on human esophageal, gastric and colorectal carcinomas. Six (55%) of the 11 gastric carcinoma cell lines and 15 (23%) of the 64 advanced gastric carcinomas showed the c-met gene amplification. Among them, c-met amplification was detected in 5 gastric cancer cell lines, derived from scirrhous gastric carcinoma and in 5 (38%) of 13 scirrhous gastric carcinoma tissues. Furthermore, patients of gastric carcinoma with c-met amplification showed significantly advanced tumor stage and poorer prognosis than those without the amplification. Conversely, no amplification was detected in any of the esophageal and colorectal carcinoma cell lines as well as carcinoma tissues except one colonic carcinoma. These results overall suggest that amplification of the c-met gene might participate in carcinogenesis and progression of stomach cancer, especially scirrhous type stomach carcinoma.

Adenocarcinoma, Scirrhous

Chondrocytic differentiation of peripheral neuroectodermal tumor cell line in nude mouse xenograft.

We have established a cell line (KU-SN) from a peripheral neuroectodermal tumor originating in the left scapula of a 4-year-old girl. The original tumor was immunoreactive with antibodies for neurofilament proteins, neuron-specific enolase, vimentin, S100 protein, and beta 2-microglobulin. Dense core granules, 50-150 nm in diameter, were identified by electron microscopy. The cell line was established from tumor cells in metastatic lung fluid. KU-SN cells were immunoreactive with the antibodies for neurofilament proteins, vimentin, neuron-specific enolase, S100 protein, glial fibrillary acidic protein, cytokeratin, and carcinoembryonic antigen. Besides these neuronal features, KU-SN cells express type 2 collagen and insulin-like growth factor 1 receptor. The addition of insulin-like growth factor 1 (100 ng/ml) increased the growth rate of KU-SN cells 2.1-fold over control. Some cells were positive for Alcian blue and alkaline phosphatase staining. Cytogenetic analysis of KU-SN cells disclosed a reciprocal chromosomal translocation [t(11,22)]. Northern blot analysis of KU-SN cells demonstrated amplified expression of the c-myc gene but not the N-myc gene. When tumor cells were transplanted into nude mice, cartilage was formed. The cartilage was immunoreactive with the antibody for HLA-ABC, indicating that it was derived from the tumor cells, not from mouse tissue. Chondrocytic differentiation was not observed in xenografts of Ewing's sarcoma cell lines SK-ES or RD-ES or the peripheral neuroectodermal tumor cell line SK-N-MC. These results indicate that KU-SN cells represent primitive neural crest cells having the potential for chondrocytic differentiation.

Animals

Antitumor activity of polysaccharide from a Chinese medicinal herb, Acanthopanax giraldii Harms.

The results of experiments with Acanthopanax giraldii polysaccharide (AGP) demonstrated that it inhibited the growth of solid Sarcoma 180 and prolonged the survival time significantly. In tumor-bearing mice, AGP enhanced the phagocytosis and chemiluminescence of macrophages. By the immunofluorescent method, binding of the third component of complement (C3) cleavage product to macrophages and proportion of C3 positive cells were increased. In crossed immunoelectrophoresis, human serum C3 was converted by AGP and appeared as the 3rd peak. The height of the 3rd peak was directly proportional to doses of AGP. The residual CH50 units of human serum decreased dose-dependently. These results suggest that the antitumor activity of AGP is related to the enhancement of immune responses.

Animals

Specificity and immunobiological properties of monoclonal antibody IMH2, established after immunization with Le(b)/Le(a) glycosphingolipid, a novel extended type 1 chain antigen.

Extended lacto-series type 1 chain antigens lacking type 2 chain core have recently been shown to comprise a new type of tumor-associated carbohydrate antigen. Examples are Le(a)/Le(a) (IV3Gal beta 1----3[Fuc alpha 1----4]Glc-NAcLc4Cer) and Le(b)/Le(a) (IV3Fuc alpha 1----2Gal beta 1----3[Fuc alpha 1----4]Glc-NAcLc4Cer) (M. R. Stroud, et al., J. Biol. Chem., 266: 8439-8446, 1991; Eur. J. Biochem., 203: 577-586, 1992). We have now established an IgG3 mouse monoclonal antibody (IMH2) after immunization of mice with Le(b)/Le(a) antigen; however, monoclonal antibody (MAb) IMH2 reacted not only with the immunogen used but also with Le(y)/Le(x) and to a lesser degree with short-chain Le(y) or Le(b) with hexasaccharide ceramide (i.e., IV2FucIII3FucnLc4Cer or IV2FucIII4FucLc4Cer). It showed a high incidence of staining and strong reactivity with carcinomas of colon, rectum, liver, pancreas, and endometrium, but no reactivity with normal colonic mucosa at various loci, and minimal reactivity with normal liver, pancreas, or uterine endometrium. On the other hand, it reacted with normal gastric mucosa, cecal mucosa, urothelium, adrenal glands, and thymus. Its expression in colorectal tumors and normal cecal tissue was independent of secretor status, whereas that in normal urothelium was dependent on secretor status. MAb IMH2 displayed strong lymphocyte-activated or complement-dependent killing of human colonic cancer Colo205 cells in vitro, and inhibition of Colo205 growth in vivo; this inhibition was comparable to that by MAb NCC-ST-421, which is directed to Le(a)/Le(a) epitope (M. Watanabe, et al., Cancer Res., 51:2199, 1991). These results indicate that a new extended type 1 chain structure, Le(b)/Le(a), is a useful tumor marker associated with carcinomas of colon, rectum, pancreas, liver, and endometrium and that MAb IMH2 has potential diagnostic or therapeutic applicability for these carcinomas.

Animals

Inhibition of DNA polymerases by tripeptide derivative protease inhibitors.

Benzyloxycarbonyl(Z)-Leu-Leu-Leu-al and dansyl(Dns)-Leu-Leu-Leu-CH2Cl, well known as protease inhibitors, effectively inhibit the activities of DNA polymerases alpha, beta and gamma from rat liver and pol I from Escherichia coli, but the ability of these inhibitors to inhibit terminal deoxynucleotidyl transferase (TdT) is weak. The mode of inhibition by these tripeptide analogues is non-competitive with dNTP. The Ki values for Z-Leu-Leu-Leu-al and Dns-Leu-Leu-Leu-CH2Cl are 6.25 x 10(-5) M and 6.56 x 10(-5) M, respectively.

Amino Acid Sequence

[Radiation management of retinoblastoma].

Forty-five patients with retinoblastoma were treated at Keio University Hospital from 1970 to 1990. Thirty-two patients had unilateral lesions and 13 had bilateral lesions. Twenty-nine patients with unilateral and 12 with bilateral lesions underwent enucleation for advanced tumor. As a result, 3 patients with unilateral retinoblastoma and all patients with bilateral disease were treated with radiotherapy (40-50 Gy) combined with or without cryotherapy and/or photocoagulation. One patient with unilateral lesion treated with radiotherapy and chemotherapy had metastases at the first visit to our clinic and was excluded from this analysis. Among 16 eyes (15 patients) treated with radiotherapy, 6 eyes had recurrence and needed retreatment. Cataract occurred in 6 of 12 eyes and good vision was preserved in 5 of 10 eyes in which function could be evaluated.

Child, Preschool

[Experimental studies on metastases from an irradiated tumor].

This study was carried out to determine the effect of irradiation of a tumor on the development of lung metastases. SANH, a spontaneous sarcoma, was isotransplanted in the right thighs of C3H mice which were either locally preirradiated (30 Gy: TBR) or non-irradiated. When the tumors had grown to 7 mm in diameter, they received 20-30 Gy of electron beams (RTx). The tumor-bearing legs were amputated at various tumor sizes, and the incidence of metastasis and number of lung nodules were compared in each treatment group. The incidences of metastases from 7 mm tumors in mice with regrowing tumors after RTx (30 Gy) and non-irradiated mice were 28% and 4%, respectively. When tumors grown in preirradiated legs were removed at 7 mm in diameter, the incidence of metastases (58%) was also enhanced by preirradiation of the tumor bed. Seven millimeter tumors that were growing in TBR legs and received RTx (20 Gy) developed a higher incidence (82%) and greater numbers of metastases than either the RTx or TBR groups. To determine the relationship between the interval of tumor bearing and development of metastases, tumors were removed at various intervals after tumor transplantation in 4 groups, namely, non-irradiated, TBR, RTx and TBR with 20 GyRTx. Lung metastases came later but increased steeply in mice given either TBR or RTx, compared with non-irradiated mice. Tumors growing in TBR and receiving RTx (20 Gy) developed many more metastases than any other group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Angiographic features of alveolar soft-part sarcoma].

The angiographic findings were analyzed in five patients with alveolar soft-part sarcoma. The angiographic appearance of the tumors was the same in all five cases: hypervascularity of the tumor including encasement, dilatation, tortuosity and displacement of feeding arteries, remarkable tumor stain and early venous filling. These angiographic findings are considered to be characteristic of alveolar soft-part sarcoma in the differential diagnosis of hypervascular soft tissue mass.

Adult

Isolation and characterization of possible target proteins responsible for neurite outgrowth induced by a tripeptide aldehyde in PC12H cells.

A tripeptide protease inhibitor, benzyloxycarbonyl-Leu-Leu-Leu-aldehyde (ZLLLal), induces the outgrowth of one or two long neurites from PC12 cells. Since this neurite outgrowth is different from that induced by nerve growth factor (NGF) in some aspects, the existence of a molecule that regulates neurite formation in PC12 cells was expected. To identify a target molecule, Leu-Leu-Leu-aldehyde (LLLal) was immobilized as a ligand for affinity chromatography. Proteins of 33-kDa, 35-kDa, and 180-kDa from the membrane and cytoplasmic fractions of PC12 cells bound specifically to the affinity column. ZLLL-COOH has no ability to induce neurite outgrowth, and the 33-kDa, 35-kDa, and 180-kDa proteins do not bind to an LLL-COOH coupled affinity column. By using the LLLal-affinity column, the 33-kDa/35-kDa proteins were found to be converted to 36-kDa/38-kDa proteins during brain development in rats. These results suggest that LLLal-binding proteins are involved in neuronal differentiation.

Animals

[Electron-microscopic study on the effect of an expandable metallic stent placement in the aortic wall].

As part of a series of basic experiments on using metallic stents for treatment of vascular stenosis, a chronological examination of changes in dog aorta following implantation of a self-expandable metallic stent was conducting using transmission and scanning electron microscopy. The Giantruco stent was placed in the abdominal aorta via the right carotid artery. One week after insertion, the aortic intima was depressed and degenerative changes observed in both endothelial and medial smooth muscle cells. After 2 weeks, except for the bend portion, the stent was covered with neointima. The neointimal surface was covered by premature endothelial cells with abundant microvilli and prominent nuclear protrusions. Under the endothelial cells, immature mesenchymal cells, such as fibroblast, were scattered throughout the edematous intercellular space. At 4 weeks, the stent was completely covered by neointima and the endothelial cells had flattened and few microvilli were in evidence. In this thickened intima, premature smooth muscle cells with myofilaments and basement membranes were observed but, around them, few collagen fibers and only occasional elastic fibers were found. At 6 weeks, the intimal surfaces were flat and smooth with a slight intimal elevation over the stent. No thrombus was observed throughout the period of the experiment. The above results indicate that dilation using metallic stents may be a useful method for treatment of vascular stenosis.

Animals

Cloning and expression of the HpaI restriction-modification genes.

The genes from Haemophilus parainfluenzae encoding the HpaI restriction-modification system were cloned and expressed in Escherichia coli. From the DNA sequence, we predicted the HpaI endonuclease (R.HpaI) to have 254 amino acid residues (Mr 29,630) and the HpaI methyltransferase (M.HpaI) to have 314 amino acid residues (37,390). The R.HpaI and M.HpaI genes overlapped by 16 base pairs on the chromosomal DNA. The genes had the same orientation. The clone, named E. coli HB101-HPA2, overproduced R.HpaI. R.HpaI activity from the clone was 100-fold that from H. parainfluenzae. The amino acid sequence of M.HpaI was compared with those of other type II methyltransferases.

Amino Acid Sequence

A monoclonal antibody capable of detecting new differentiation antigen of the stomach.

A monoclonal antibody (MAb) was raised against a gastric adenocarcinoma cell line TMK-1 that shows parietal cell differentiation. This MAb, an IgMK, named 20DII, reacted immunohistochemically with the intracytoplasmic secretory canalicular membranes of normal parietal cells of the stomach. In the fetal stomach at 4 months of gestation, the luminal surface of fundic epithelia and developing parietal cells had MAb20DII immunoreactivity, but at 6 months of gestation only parietal cells showed immunoreaction. Out of 133 gastric carcinomas, 98 (74%) had MAb20DII immunoreactivity. In the well-differentiated type, immunoreactivity was localized at the luminal surface of tumor cells and, in the poorly differentiated type, in the intracytoplasmic tubulovesicles of tumor cells. In Western-blot analysis, the antigenic molecule had a molecular weight exceeding 300 kDa in the tumor tissues, but only a 62-kDa immunoblot band was seen in the corresponding non-cancerous gastric mucosa. However, there was no correlation between the expression of high-molecular-weight antigens and the histological types of gastric carcinoma. These results suggest that 20DII antigen may be involved in differentiation of parietal cells in the fetal stomach and in stomach cancer.

Adenocarcinoma

Glial fibrillary acidic protein (GFAP) expression and nucleolar organizer regions (NORs) in human gliomas.

The frequency of nucleolar organizer regions (NORs) in each glioma tissue and the relation between the expression of glial fibrillary acidic protein (GFAP) and the frequency of NORs was investigated. The number of Ag-NORs per cell for glioblastoma multiforme was significantly higher than that for anaplastic astrocytoma (P less than 0.05) and that for astrocytoma (P less than 0.01). The number of Ag-NORs per cell for GFAP-positive cells was significantly lower than that for GFAP-negative cells in each histopathological grade (P less than 0.01). Moreover, the linear relationship was demonstrated between the Ag-NORs numbers of GFAP-negative cells and bromodeoxyuridine (BUdR) labeling indices. From these results, it is concluded that many GFAP-positive glioma cells may have low growth potential in glioma tissue and GFAP-negative cells may have a close relation to cell proliferation. The combination of immunohistochemical and silver colloid staining is a useful method for investigating the biological characteristics of brain tumors.

Astrocytoma

Growth inhibition of transforming growth factor beta on human gastric carcinoma cells: receptor and postreceptor signaling.

The effect of transforming growth factor beta (TGF-beta) on human gastric carcinoma cell lines was examined. Cell growth and DNA synthesis of TMK-1 were inhibited by TGF-beta, whereas MKN-28 presented no response to TGF-beta. Scatchard plot analysis of TGF-beta binding showed that TMK-1 had a relatively small number of high-affinity receptors, whereas MKN-28 had a large number of low-affinity receptors. By affinity labeling, only the type I receptor (Mr 65,000) for TGF-beta was detected in TMK-1, while three types of receptors, type I, type II (Mr 85,000-95,000), and type III (Mr 250,000-350,000), for TGF-beta were present in MKN-28. TGF-beta treatment reduced p34cdc-2 kinase activity and the level of phosphorylation of retinoblastoma protein in TMK-1, whereas it did not affect them in MKN-28. mRNAs for MYC and platelet-derived growth factor B chain were increased by treatment of TGF-beta on TMK-1. cAMP-responsive element binding activity was decreased by TGF-beta treatment in MKN-28 but not in TMK-1. This was closely correlated with protein kinase C activity. These results suggest that the type I receptor for TGF-beta in human gastric carcinoma cells may be mainly linked with the growth inhibition of TGF-beta by a decrease in retinoblastoma protein phosphorylation by p34cdc-2 without suppression of MYC expression. Conversely, TGF-beta may reduce protein kinase C activity and cAMP-responsive element binding activity in TGF-beta-resistant gastric carcinoma cells.

CDC2 Protein Kinase

Calbindin-D28k in the basal ganglia of patients with parkinsonism.

An immunohistochemical study was carried out to investigate the topographic distribution of calbindin-D28k in the human basal ganglia and substantia nigra and its alterations in patients with idiopathic Parkinson's disease (PD), parkinsonism-dementia complex on Guam, progressive supranuclear palsy, and striatonigral degeneration. In normal control subjects, calbindin-D28k immunoreactivity was identified in the medium-sized neurons and neuropil of the matrix compartment of the striatum, the woolly fiber arrangements of the globus pallidus, and the fiber structures of the pars reticulata of the substantia nigra. Calbindin-D28k expression in the basal ganglia of patients with PD and parkinsonism-dementia on Guam was not different from that of control subjects, suggesting that the matrical output pathway is spared in these disorders. In contrast, its disruption is inferred from the observed disorganization of woolly fibers in the globus pallidus of patients with progressive supranuclear palsy and the reduced calbindin-D28k reactivity in the putaminal matrix and the pars reticulata of the substantia nigra of subjects with striatal degeneration. Thus, our results indicate that calbindin-D28k is a useful marker for the projection system from the matrix compartment and that its expression is modified in patients with progressive supranuclear palsy and striatal degeneration.

Aged

Coronary angioplasty using an over-the-wire balloon catheter through a new 6 French guiding catheter.

A new 6 French (F) guiding catheter with a large, teflon-coated internal lumen (4.2F) was developed, permitting use of the standard ultralow profile (less than 3F) over-the-wire system. This small coronary angioplasty system (6F-PTCA) was evaluated in 48 lesions in 45 of 137 patients (33%) who underwent coronary angioplasty between September 1990 and January 1991. The mean age was 64 years (range 49 to 82); 37 (82%) were male. The procedure was via the brachial artery in 28 patients (62%). The overall primary success rate was 96%. It was 100% via the brachial artery and 90% via the femoral artery. There were no major complications. The puncture compression time with the 6F-PTCA via the brachial artery and via the femoral and with 8F-PTCA via the femoral was 3.8, 9.6, and 16.9 hr, respectively (P less than 0.001), although the procedure time of the 6F-PTCA via brachial and via femoral and of the 8F-PTCA was not significantly different. The mean hospital stay was 3.1, 4.5, and 5.5 days, respectively (P less than 0.01). A small hematoma occurred in 2 patients (4.4%) after the 6F-PTCA and in 3 (3.3%) after 8F-PTCA, and a large hematoma (greater than 5 cm) was noted in 7 patients (7.6%) after 8F-PTCA. These results indicate that coronary angioplasty using the over-the-wire system through the new 6F guiding catheter is technically feasible. Moreover, this approach, especially when advanced via the brachial artery, could shorten the hemostasis time and facilitate early ambulation.

Aged