Biomedical subjects

T Hida

Publications and source records attributed to T Hida.

At least 91 records · Page 5Linked to original sources

PubMed1994

Histochemical and immunohistochemical studies on keratan sulfate in the anterior segment of the developing human eye.

Changes in the distribution of keratan sulfate in the anterior segment of developing ocular tissue were investigated histochemically and immunohistochemically using human eyes from 5 weeks gestation to 2 years after birth. Enzyme digestion methods with streptomyces hyaluronidase, chondroitinase and keratanase showed that the main component of glycosaminoglycans in the cornea was hyaluronic acid at the early stage and chondroitin sulfate from the middle stage to the neonatal stage. Keratan sulfate was found at the neonatal stage. Immunohistochemical staining, however, showed that keratan sulfate was present from 6 weeks around mesenchymal cells which migrated into the anterior portion. The stroma and endothelial cells of the cornea, trabecular tissue, iris, choroidal tissue of the ciliary body and anterior tunica vasculosa lentis were the next tissues to show positive for immunostaining. Keratan sulfate became limited to the cornea and lumbus and mostly disappeared from the other anterior segment tissues after birth. These findings suggest that tissues which seem to originate from mesenchymal cells and surround the chamber space contain keratan sulfate during the developmental stage.

Adolescent↗

PubMed1994

Augmentation of host defense mechanisms against tumor by sperabillin polymers, new basic peptidyl biopolymers, in mice.

Sperabillin polymers, which have been shown recently to have antitumor activity, are new basic peptidyl polymers composed of a pseudo-peptide antibiotic, sperabillin A. The polymers, HP-2 (MW 9990), AP-2 (MW 20,100) and AB-2 (MW 35,000), were found to potently activate murine peritoneal macrophages. The phagocytosis-dependent respiratory burst and Fc gamma receptor expression of peritoneal macrophages from C57BL/6 mice were enhanced after in vitro cultivation with these polymers. When HP-2, a representative of these polymers, was intraperitoneally injected into mice, the number of peritoneal exudate cells increased and phagocytosis-dependent respiratory burst and class II (I-A) antigen expression of peritoneal macrophages were augmented. These macrophages showed strong inhibitory activity against the growth of murine tumor cell lines such as EL4 lymphoma and B16 melanoma. Nitrogen oxide, tumor necrosis factor (TNF) and interleukin 1 (IL-1) might be required for this inhibitory activity. Moreover, in mice treated with HP-2, splenocyte counts also increased and non-specific killer activity of the splenocytes was augmented. These results indicate that sperabillin polymers are new macrophage activators.

Adjuvants, Immunologic↗

PubMed1994

Inhibition by gomisin A, a lignan compound, of hepatocarcinogenesis by 3'-methyl-4-dimethylaminoazobenzene in rats.

The effects of gomisin A, a lignan compound of Schizandra fruits, on hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) in rats were investigated. Gomisin A inhibited both increases of the number and size of glutathione S-transferase placental form (GST-P)-positive foci, a marker enzyme of preneoplasm, and the population of diploid nuclei, as a proliferative state of hepatocytes, in the liver from rats simultaneously treated with 3'-MeDAB. Gomisin A increased GST activity in the liver, by raising the level of GST 1 and 2 isozymes. 3'-MeDAB increased GST activity and GST-P expression. This high level of GST-P induced by 3'-MeDAB was suppressed by additional treatment with gomisin A. In an experiment on simultaneous treatment, gomisin A increased the biliary excretion of 3'-MeDAB-related aminoazo dyes and decreased the content in the liver of rats fed with 0.06%-3'-MeDAB containing diet. In an experiment on pretreatment with 3'-MeDAB, even though no aminoazo dye was detectable in the liver or bile 2-weeks after cessation of 3'-MeDAB-feeding, gomisin A showed a tendency to reduce the preneoplastic changes of increases in GST-P positive foci and diploid nuclei in the liver. These results suggest that gomisin A inhibits the hepatocarcinogenesis induced by 3'-MeDAB by enhancing the excretion of the carcinogen from the liver and by reversing the normal cytokinesis.

Animals↗

PubMed1994

Novel retrovirus protease inhibitors, RPI-856 A, B, C and D, produced by Streptomyces sp. AL-322.

Four kinds of retrovirus protease inhibitors (RPI-856 A, B, C and D) were isolated as white powder from the culture filtrate of a soil isolate, Streptomyces sp. AL-322 by column chromatography using Diaion HP-20, Sephadex LH-20, ODS reversed phase HPLC and SP-2SW ion exchange HPLC. The structures of these inhibitors were elucidated by physico-chemical properties, chemical reactions and spectral analyses, as valyl-ADPAA-leucyl-AOPBA-valyl-valyl-aspartic acid (RPI-856 A and B) and valyl-ADPAA-leucyl-AOPBA-valyl-valine (RPI-856 C and D) [ADPAA = 2-amino-2-(3,5-dihydroxyphenyl)acetic acid, AOPBA = 3-amino-2-oxo-4-phenylbutyric acid]. RPI-856 A and B, and RPI-856 C and D were both determined to be diasteromers each other on the asymmetric carbon in AOPBA. These four inhibitors strongly inhibited in vitro HIV-1 protease and HTLV-I protease both derived from recombinant Escherichia coli with IC50 of 10(-7) approximately 10(-8) M.

Amino Acid Sequence↗

PubMed1994

Structures of dnacin A1 and B1, new naphthyridinomycin-type antitumor antibiotics.

Dnacin A1 and B1 were revealed to be new naphthyridinomycin-type antitumor antibiotics with formulae of C20H23N5O4 and C19H24N4O5, respectively. The gross structure of dnacin A1 was elucidated by the spectroscopic analyses. Conversion of dnacin B1 into A1 by treatment with potassium cyanide indicated the presence of an alpha-carbinolamine moiety in dnacin B1. The relative stereochemistry of dnacins was clarified by analysis of the NOESY spectra.

Antibiotics, Antineoplastic↗

PubMed1994

Evaluation of biological characteristics of lung cancer by the human 28 kDa vitamin D-dependent calcium binding protein, calbindin-D28k.

We evaluated the biological characteristics of lung cancer by measuring their contents of human 28 kDa vitamin D-dependent calcium binding protein (calbindin-D). Calbindin-D concentrations were determined in tumor tissue and normal lung tissue extracts from patients with lung cancer by enzyme immunoassay. The percentage of high calbindin-D containing tissues in small cell lung cancer (SCLC) was significantly higher than that in non-small cell lung cancer (NSCLC) and the calbindin-D concentration was low in normal lung extracts. In addition, most of the NSCLC which had a significantly high level of calbindin-D were at the advanced cancer stage with lymph node metastasis. Calbindin-D concentrations were also determined in lung cancer cell lines. The percentage of high calbindin-D containing cell lines was high in classic type SCLC, followed in order by variant type SCLC and NSCLC. In addition, in order to examine the usefulness of calbindin-D as a marker of neuroendocrine properties of lung cancer, we compared the sensitivity and specificity of calbindin-D for distinguishing classic from variant type SCLC with neuron-specific enolase (NSE) and aromatic L-amino acid decarboxylase (AADC) by relative operating characteristic curves. The diagnostic accuracy of AADC was the highest of the three and that of calbindin-D was as high as that of NSE. These findings suggest calbindin-D to be related to the neuroendocrine properties of lung cancer.

Aromatic-L-Amino-Acid Decarboxylases↗

PubMed1994

[Report of two cases with idiopathic true exfoliation of the lens capsule--histopathological and electron microscopical study].

True exfoliation is a delamination of the superficial or all layers of the anterior lens capsule, appearing as a transparent membrane in the anterior chamber. It is a rare occurrence and most of the reported cases have been associated with histories of exposure to excessive heat, ocular trauma, or intraocular inflammation. We report two cases of idiopathic true exfoliation without any contributory history. In one case, the lens was surgically removed intracapsularly, and served for histological study and scanning and transmission electron microscopy. The anterior fourth of the capsule was delaminated. Underlying epithelial cells showed nonspecific senile changes.

Aged↗

PubMed1993

Recombinant human stem cell factor mediates chemotaxis of small-cell lung cancer cell lines aberrantly expressing the c-kit protooncogene.

Accumulating evidence suggests that c-kit and its ligand, stem cell factor (SCF), play an important role in the regulation of at least three lineages of stem cell growth and possibly in leukemogenesis, while only limited data are available that suggest possible involvement of c-kit/SCF in the development of human solid tumors such as lung cancer. We have recently reported that c-kit is aberrantly expressed almost exclusively in small-cell lung cancer (SCLC) among various types of solid tumors. The present study revealed that c-kit protein ectopically expressed in SCLC is indistinguishable from that in leukemia cell lines with megakaryocytic characteristics with respect to amount, molecular size, and autophosphorylation status in response to recombinant human SCF. Furthermore, significant chemotactic response as well as moderate in vitro cell growth was induced in SCLC cell lines by the addition of recombinant human SCF, suggesting that c-kit/SCF may play an important biological role in the development of SCLC. Our extensive search for activating mutations naturally occurring in the c-kit gene revealed an amino acid substitution in the transmembrane domain of an SCLC cell line, although the functional consequences of this variant allele are yet to be determined.

Carcinoma, Small Cell↗

PubMed1993

Chemistry and anti-tumor activity of sperabillin polymers.

Sperabillin A, 3-[[(3R,5R)-3-amino-6-[(2E,4Z)-2,4-hexadienoylamino]- 5-hydroxyhexanoyl]amino]propanamidine dihydrochloride, was polymerized on standing for several days under a highly humid atmosphere or in the presence of radical initiators. The average molecular weight of the polymers obtained could be regulated by changing the reaction conditions in the latter case. Spectral analyses of the polymers revealed that the 2,4-hexadienoyl moiety of sperabillins was polymerized in a free radical-initiated reaction. The polymers selectively inhibited the proliferation of human umbilical vein endothelial (HUVE) cells. Polymers having higher molecular weight showed stronger inhibition of HUVE cell proliferation. In addition, the polymers showed anti-tumor activity against B16 melanoma in vivo.

Amidines↗

PubMed1993

Synchronous lung cancer presenting with small cell carcinoma and adenocarcinoma.

We describe a case of synchronous primary lung cancer presenting with small cell carcinoma and adenocarcinoma, in which expression of the cell surface antigens and also tumor markers were evaluated immunohistologically. A review of the literature concerning synchronous or metachronous primary lung cancers is also presented.

Adenocarcinoma↗

PubMed1993

TAN-1120, a new anthracycline with potent angiostatic activity.

A potent angiogenesis-inhibitory compound TAN-1120 was found to be produced by a Streptomyces species isolated from a soil sample. The producing organism was characterized as a new subspecies of S. triangulatus and named S. triangulatus subsp. angiostaticus subsp. nov. due to its specific ability to produce the compound. This substance was isolated as a red powder by a combination of organic solvent extraction, silica gel column chromatography and preparative HPLC using an ODS column. Its structure was elucidated by chemical reactions and spectral analyses to be a new baumycin-group anthracycline. Reduction of TAN-1120 gave two compounds, a deoxy derivative and baumycin A1. TAN-1120 showed remarkably potent angiostatic activity in two conventional angiogenesis assay systems in vivo, while doxorubicin and daunomycin had far weaker activity. It strongly inhibited proliferation of vascular endothelial cells did not prevent capillary cord formation in vitro by the endothelial cells on extracellular matrix-coated plates. TAN-1120 is one of the most potent angiostatic agents reported.

3T3 Cells↗

PubMed1993

Synthesis and antimicrobial activity of sperabillin derivatives.

Modification of sperabillins was carried out. The 2-amidinoethylamino moiety was removed by brief acidic hydrolysis. The 2,4-hexadienoyl moiety was hydrogenated to the hexanoyl moiety and this was cleaved by an enzymatic reaction using the cells of Pseudomonas acidovorans IFO 13582. The 2-amidinoethylamino and the 2,4-hexadienoyl moieties were replaced with other groups. The derivative which was prepared by condensation of two molar amounts of dehexadienoylsperabillin A with (E,E)-muconic acid showed better protective effects than sperabillin A against Gram-negative bacteria.

Amidines↗

PubMed1993

[Histochemical and electron microscopic study of the formation of trabecular meshwork and changes of glycosaminoglycans].

The development of iridocorneal angle and trabecular tissue was investigated histochemically and electron microscopically. Sixty-three human eyes at from 5 to 22 weeks of gestation were used in this study. For identifying glycosaminoglycans, alcian blue staining and enzyme digestion methods with hyaluronidase and chondroitinase AC and ABC were carried out light microscopically. Electron microscopically, specimens were stained with ruthenium red. In the early stage from 8 to 10 weeks, mesenchymal cells between the primordium of the cornea and the iris became elongated and connected with one another. Desmosome-like junctional complexes were observed in these cells. Schlemm's canal and para-canalicular tissue were observed at 20 weeks and the structure of the meshwork became similar that of adults. From findings of enzyme digestion methods, glycosaminoglycans in trabecular tissue seemed to be mainly hyaluronic acid in the early stage, which was replaced by chondroitin sulfate and dermatan sulfate afterwards. Substances positive for ruthenium red, which seemed to be glycosaminoglycans, was observed in intercellular spaces electron microscopically. They decreased according to development. These findings indicated that the beginning of aqueous outflow might be related to the decrease of glycosaminoglycans in trabecular tissue.

Gestational Age↗

PubMed1993

Glutathione S-transferase pi levels in a panel of lung cancer cell lines and its relation to chemo-radiosensitivity.

The human placental form of glutathione S-transferase pi (GST-pi) was measured by a sandwich enzyme-linked immunosorbent assay in lung cancer cell lines established in our laboratories. In classic-type small cell lung cancer (SCLC), variant-type SCLC and non-small cell lung cancer (NSCLC), the respective mean GST-pi values were 0.83 +/- 0.88, 3.27 +/- 2.85 and 2.40 +/- 0.76 micrograms/mg protein. Cell lines with high GST-pi content had low levels of neuron specific enolase, which is known as a representative tumor marker for SCLC. This suggests that GST-pi may also be used as a potential marker for NSCLC. The lines with low GST-pi content were more sensitive to radiation than those with high GST-pi content. Cell lines not subjected to prior therapy also showed a good correlation between GST-pi levels and chemosensitivity to cisplatin. The findings suggest that GST-pi can be used as an adjunctive marker for lung cancer.

Carcinoma, Non-Small-Cell Lung↗

PubMed1993

[Antigen phenotype of lung cancer and its relation to chemo-radiosensitivity].

Phenotypic heterogeneity in lung cancer was investigated immunochemically, using monoclonal antibody NE150, PE35 and OE130. The presence of NE150 neuroendocrine and PE35 panepithelial antigens and the absence of another epithelial antigen, OE130, i. e., NE150+/PE35+/OE130- is the typical phenotype of small cell lung cancer, while NE150-/PE35+/OE130+ is that of non-small cell lung cancer. The results obtained from the cell lines with no prior therapy indicated a good correlation between the antigen phenotype and chemo-radiosensitivity, suggesting that antigen phenotype may reflect some intrinsic resistance which could be related to differentiations in the status of the lung cancer.

Antibodies, Monoclonal↗

PubMed1992

Wild-type but not mutant p53 suppresses the growth of human lung cancer cells bearing multiple genetic lesions.

Accumulating evidence indicates that lung cancer arises due to multiple genetic changes in both dominant oncogenes, such as ras, and tumor suppressor genes, such as p53. In this report we examined whether the wild-type p53 gene is able to suppress in vitro and/or in vivo cellular growth of lung cancer cell lines which carry multiple genetic abnormalities. Introduction of a wild-type p53 complementary DNA expression vector into lung cancer cell lines carrying either a homozygous deletion (NCI-H358) or a missense mutation (NCI-H23) in the p53 gene greatly suppressed tumor cell growth. In contrast, p53 expression vectors bearing lung cancer derived mutations affecting single amino acids had lost this growth suppressing ability.

Animals↗

PubMed1992

The lack of an effect of intraocular steroids on irradiated fibroblasts in experimental proliferative vitreoretinopathy.

Contraction of intraocular membranes is an important event in the development of proliferative vitreoretinopathy (PVR). When sufficient numbers of cells are present in the vitreous cavity, the retina usually detaches as a result of the contractive force generated by these cells. Steroids reduce the occurrence of retinal detachments in rabbit models of PVR by inhibiting the proliferation of injected fibroblasts. In this study, we used non-proliferative, irradiated cells to determine a possible effect of steroids on preretinal membrane contraction in PVR. We found no clinical difference between steroid treated eyes and sham-treated control eyes. Surgical reduction of the contractile tissue and medical therapy to prevent reproliferation are necessary in order to treat PVR effectively.

Animals↗

PubMed1992

Complex intrachromosomal rearrangement in the process of amplification of the L-myc gene in small-cell lung cancer.

The L-myc gene was first isolated from a human small-cell lung cancer (SCLC) cell line on the basis of its amplification and sequence similarity to c-myc and N-myc. A new mechanism of L-myc activation which results from the production of rlf-L-myc fusion protein was recently reported. On the basis of our earlier observation of a rearrangement involving amplified L-myc in an SCLC cell line, ACC-LC-49, we decided to investigate this rearrangement in detail along with the structure of L-myc amplification units in five additional SCLC cell lines. We report here the identification of a novel genomic region, termed jal, which is distinct from rlf and is juxtaposed to and amplified with L-myc during the process of DNA amplification of the region encompassing L-myc. Long-range analysis using pulsed-field gel electrophoresis revealed that the amplified L-myc locus is involved in highly complex intrachromosomal rearrangements with jal and/or rlf. Our results also suggest that the simultaneous presence of rearrangements both in rlf intron 1 and in regions immediately upstream of L-myc may be necessary for the expression of rlf-L-myc chimeric transcripts.

Carcinoma, Small Cell↗