Biomedical subjects

T Kosaka

Publications and source records attributed to T Kosaka.

At least 199 records · Page 11Linked to original sources

PubMed1991

The expression of proliferative-associated nuclear antigen p105 in gastric carcinoma.

The expression of proliferation-associated nuclear antigen p105 of gastric carcinomas was studied by multiparameter flow cytometric and immunohistochemical technique. Multiparameter flow cytometric analysis revealed that p105 expression was rarely observed in the resting cells of normal gastric epithelium. On the contrary, the immunofluorescence (IF) intensity of cancer cells in G1 phase was approximately two-fold to three-fold greater than that of G0 phase of cancer cells or normal gastric epithelium. The p105 antigen content of cancer cells increased with cell cycle progression, and increased more rapidly in cells in late S-phase than in cells in G0 and early S-phase. Microphotometric study demonstrated that cells in M-phase exhibited a dramatic increase in the amount of the antigen, and the IF intensity of the mitotic cells were approximately five-fold to ten-fold greater than that of cells in G1 and S-phase. These results indicate that the antigen demonstrated by the p105 monoclonal antibody is present in the G1, S, G2, M-phases, but not in the G0 phase. Immunohistochemical technique demonstrated that patients with lymph node metastases are more likely to have high p105-positive rates than did node-negative patients. The mean p105-positive rates of aneuploid tumors was significantly higher than those of diploid tumors. From these results the authors speculate that the measurement of p105-positive rates may be a powerful prognostic indicator of gastric carcinoma.

Antigens, Neoplasm↗

PubMed1991

Amsacrine-induced lesions in DNA and their modulation by novobiocin and 2,4-dinitrophenol.

The cancer chemotherapeutic agent amsacrine, 4'-(9-acridinylamino)-methanesulfon-m-anisidide (mAMSA), is thought to effect cytotoxicity by inhibiting the ATP-dependent enzyme topoisomerase II in the act of its duplex strand-passing action. Upon protein denaturation, the arrested "cleavable complex" that results gives rise to double- and single-strand breaks (dsbs and ssbs) and DNA-protein cross-links (dpcs). Simultaneous cotreatments with 2,4-dinitrophenol (DNP) or novobiocin (novo) abrogates mAMSA cytotoxicity in Chinese hamster cells (H. Utsumi et al., Cancer Res., 50:2577-2581, 1990). Pulsed-field gel electrophoresis was used to estimate dsbs, velocity sedimentation in alkaline sucrose gradients for ssbs, and alkaline elution without protease digestion for dpcs. Although cotreatment with DNP or novo modulated somewhat the yield of DNA lesions due to mAMSA, quantitatively these changes did not correlate at all with, and therefore could not account for, the reduced lethality that resulted from cotreatments. For example, DNA cotreatment markedly increased the yields of dsbs, ssbs, and dpcs, even though cell killing was appreciably reduced. Furthermore, neither DNP nor novo cotreatment affected the rate, or the completeness of, the repair of mAMSA-induced DNA damage, and neither cotreatment lowered total cellular ATP. Hence, the arresting of the cleavable complex by mAMSA, made evident by lesions in DNA, did not correlate with cytotoxicity. However, cotreatment with either DNP or novo resulted in an enhanced recovery of the mAMSA-induced inhibition of replicative DNA synthesis. Because DNP and novo (transiently) slow down DNA synthesis, it is proposed that these compounds abrogate mAMSA killing of S phase cells by reducing the disorganization of the processing of replicated DNA by topoisomerase II.

2,4-Dinitrophenol↗

PubMed1991

Tyrosine hydroxylase-like immunoreactive neurons in the olfactory bulb of the snake, Elaphe quadrivirgata, with special reference to the colocalization of tyrosine hydroxylase- and GABA-like immunoreactivities.

The distribution and structural features of tyrosine hydroxylase-like immunoreactive (TH-LI) neurons were studied in the olfactory bulb of a snake, Elaphe quadrivirgata, by using pre- and post-embedding immunocytochemistry at the light microscopic level. In contrast to rodent olfactory bulbs previously reported, many TH-LI neurons were seen not only in the main olfactory bulb (MOB) but also in the accessory olfactory bulb (AOB). With regard to the TH-like immunoreactivity, there appeared no appreciable differences between MOB and AOB. As in mammalian MOB, the majority of TH-LI neurons were clustered in the periglomerular region and appeared to send their dendritic branches into glomeruli, which as a whole make an intense TH-LI band in the glomerular layer (GML). In the external plexiform/mitral cell layer (EPL/ML) of MOB and AOB as well as in the outer sublamina of the internal plexiform layer (OSL) of AOB, an appreciable number of TH-LI neurons were scattered, extending dendritic processes which appeared to make a loose meshwork. TH-LI neurons in EPL/ML (including OSL) appeared to consist of at least two morphologically different types. The first had a small perikaryon and one or two smooth dendrites which usually extended to GML and were frequently confirmed to enter into glomeruli. The second had a larger perikaryon and 2-3 dendrites which branched into several varicose processes extending in EPL/ML/OSL but appeared not to enter into glomeruli. The TH-like immunoreactivity was rarely seen in the internal plexiform layer and internal granule cell layer. The colocalization of GABA-like and TH-like immunoreactivities was further studied. Almost all TH-LI neurons in both EPL/ML/OSL and GML contained GABA-like immunoreactivity irrespectively of the type of TH-LI cells.

Animals↗

PubMed1991

Proliferation-associated nuclear antigen p105 as a marker for metastasis of human gastric cancer.

The expression of the proliferation-associated nuclear antigen p105 in 43 patients with advanced gastric carcinoma was studied by multiparameter flow cytometry. The p105 immunofluorescence intensity of tumor cells in the G0G1 phase was 1.8-14.5 times that in stromal cells, and the stromal cells could be separated by flow cytometry. The p105 intensity, which is the ratio of the mean fluorescence intensity of cancer cells to that of stromal cells in the G0G1 phase, was not correlated with the DNA index, the size of the S-phase fraction, or the histological type of the tumor. However, the intensity was significantly greater in patients with hepatic metastasis and significantly lower in patients with peritoneal metastasis. The patients with a p105 intensity of 4.0 or more had a significantly higher incidence of hepatic metastasis (8/22; 36%). The patients with a p105 intensity of less than 4.0 had a significantly higher incidence of peritoneal metastasis (8/21; 38%). These results suggest that the p105 intensity is a marker of metastasis useful in the treatment and follow-up of patients.

Biomarkers, Tumor↗

PubMed1991

Clinical significance of tumor marker NCC-ST 439 in large bowel cancers.

We examined serum NCC-ST 439 for its significance as a tumor marker of large bowel cancer in 121 patients with primary and 36 with recurrent large bowel cancer. Serum NCC-ST 439 was positive in 27.3 percent of the former and 66.7 percent of the latter. It was false-positive in only 5.6 percent of patients with benign diseases. Positive serum NCC-ST 439 correlated with lymph node and liver metastases. The combination assay for NCC-ST 439, CEA, and CA19-9 was positive in 49.6 percent of the patients with primary tumors and 88.9 percent of those with recurrent tumors; in other words, the diagnostic accuracy improved. The results demonstrated that the determination of serum NCC-ST 439 in large bowel cancer might be useful in cancer staging and that NCC-ST 439, if used in combination with CEA, is particularly useful in diagnosing recurrences because of its improved diagnostic accuracy.

Antibodies, Monoclonal↗

PubMed1991

Detection by CT during arterial portography of colorectal cancer metastases to liver.

A prospective evaluation of the accuracy of real-time ultrasonography (US), computed tomography (CT), infusion hepatic angiography (IHA), and computed tomography during arterial portography (CT-AP) was performed on 65 resected liver metastases of colorectal cancers. The total detection rate was 58.5 percent for US, 56.3 percent for CT, 55.4 percent for IHA, and 86.2 percent for CT-AP. The sensitivity of 29 lesions with diameters of smaller than 1 cm was 65.5 percent for CT-AP, CT found only two, and both US and IHA localized no more than three. The smallest lesions detectable by CT-AP were as small as 0.4 cm in diameter. CT-AP proved most useful in detecting the liver metastases, and the use of this technique is recommended for preoperative planning of hepatectomy on patients with liver metastases.

Angiography↗

PubMed1991

Antibodies against Tetrahymena 14-nm filament-forming protein recognize the replication band in Euplotes.

Tetrahymena 14-nm filament-forming protein (49K protein) is a structural protein which is involved in activity of the pronuclei during conjugation (O. Numata, T. Sugai, and Y. Watanabe (1985) Nature (London) 314, 192-194). Using monoclonal and polyclonal antibodies, we here demonstrate the presence of a cross-reactive protein (CRP-49) within the macronuclear replication bands of Euplotes harpa and E. eurystomus which is recognized by anti-49K protein antibodies. Immunoblotting reveals that both monoclonal and polyclonal antibodies cross-react to a protein with an apparent molecular mass of 50 kDa in an E. harpa cell extract and to a protein of 49 kDa in a macronuclear extract of E. eurystomus. The antibodies used in this study have no effect upon in vitro DNA synthesis in the replication band of E. eurystomus.

Animals↗

PubMed1991

Reparability of DNA double-strand breaks and radiation sensitivity in five mammalian cell lines.

We examined the relationship between gamma-ray-induced DNA double-strand breaks (dsb) and cell lethality in five mammalian cell lines differing in radiosensitivity; HA-1, HMV-I, L5178Y, M10 and LX830. These cells were derived from Chinese hamster, human melanoma, and mouse lymphoma (parent and its radiosensitive mutants), respectively. HA-1 cells were the most radioresistant and LX830 cells were the most radiosensitive among these five lines. Although the induction of dsb by gamma-rays for HA-1 was significantly different from other curves (p less than 0.05 for HMV-I and p less than 0.01 for L5178Y and M10), those for the other four lines were similar to one another. In addition, the most radioresistant cell line, HA-1, showed the highest dsb induction among five cell lines. Therefore, there is no correlation between radiosensitivity and the induction of dsb in these five lines. On the other hand, residual dsb after repair incubation (non-reparable dsb) do differ from each other. When the relative number of non-reparable dsb was plotted against the radiation dose, the dose-response curves for all the cell lines were concave, and the slopes of curves for M10 and LX830 were steeper than those for other cell lines. These curves are a mirror-image of the survival curves. The results suggest that there is a correlation between the radio-resistance in terms of cell killing and the capacity of cells to repair dsb.

Animals↗

PubMed1991

Expression of endothelin-2 (ET-2) gene in a human renal adenocarcinoma cell line: purification and cDNA cloning of ET-2.

It has been found that human renal adenocarcinoma ACHN cells synthesize and secrete immunoreactive endothelin (ir-ET) in the culture medium. Partial characterization of this material with reverse-phase high-performance liquid chromatography (RP-HPLC) suggested that ACHN cells synthesized only human endothelin-2 (ET-2). Isolation and characterization of this ir-ET-2 has revealed that this peptide has almost the same amino acid sequence and molecular weight as that of human ET-2 deduced from the nucleotide sequence of cloned human ET-2 gene. To delineate the precise structure of human ET-2 precursor, ET-2 cDNAs were cloned from a cDNA library constructed with mRNA derived from the ACHN cells, and the nucleotide and deduced amino acid sequences were determined. The ET-2 cDNA that has the longest open reading frame encodes prepro-ET-2 protein, consisting of 178 amino acid residues. The ET-like sequence found in the prepro-ET-1 and -ET-3 was also conserved in this prepro-ET-2. The Northern blot analysis of mRNA revealed that the transcript of the human ET-2 gene was 1.4 kb.

Adenocarcinoma↗

PubMed1991

Expression of arginase by mouse myeloid leukemic cell differentiation in vitro induced with tumor necrosis factor.

Induction of arginase activity in mouse myeloid leukemic M1 cells by treatment with recombinant human tumor necrosis factor (rH-TNF) or TNF-elicited mouse serum (TNS) were examined in vitro. M1 cells differentiated into macrophage-like cells by addition of rH-TNF or TNS. The differentiated cells expressed phagocytic function and did not grow anymore. Cytolytic effect of rH-TNF or TNS was not observed. The differentiation of M1 cells into phagocytic cells by the TNS treatment was more rapidly than that by the rH-TNF treatment though TNS contained 25-time less amounts of TNF indicating species specificity of TNF action on myeloid leukemic cells or TNS containing other differentiation factor(s). 3H-ornithine formation from 3H-arginine is catalyzed by arginase (EC. 3.5.3.1). The enzyme product increased in the M1 cell culture medium by the treatment with rH-TNF or TNS. The arginase activity statistically correlated with the appearance percentage of differentiated cells with phagocytic function. These results suggest that in vitro differentiation of M1 cells is accompanied by induction of arginase activity.

Animals↗

PubMed1991

[Study of para-aortic lymph node metastasis for advanced gastric cancer on consecutive lymph node slices].

Para-aortic lymph nodes (No. 16) from 21 patients with advanced gastric cancer who underwent extensive lymph node dissection, were sliced consecutively at intervals of 50 mu to study minute metastasis of No. 16 lymph nodes. Twenty-six of 30 metastatic lymph nodes had minute involvement, in which carcinoma cells were detected in marginal sinus of lymph node, microscopically. The rate of the metastases to No. 16 lymph nodes was 19% among N0-3 cases by conventional method (not consecutive slices). On the contrary, the percentage of metastasis to No. 16 lymph nodes by consecutive slices was 33% among N0-3 cases. Therefore, No. 16 nodes are involved in metastasis at high rate at operation and the extensive lymph node dissection including No. 16 nodes (R4) will be recommended to prevent lymph node recurrence caused by such a minute metastasis.

Aorta↗

PubMed1991

Relation of proliferative activity to survival in patients with advanced gastric cancer.

The proliferative activities of 98 biopsied specimens of advanced gastric cancers were measured by the in vitro bromodeoxyuridine (BrdU) labelling method. BrdU labelling indices (LIs) varied from 4.8 to 45.1%. There was no correlation of BrdU LIs and histological type, distant metastasis, serosal invasion, macroscopic type or tumor size. However, BrdU LIs of tumors with lymph node metastases were significantly higher than those without them. Patients with tumors showing high BrdU LIs had a three-fold relative risk of death, as compared with those showing low BrdU LIs. When the BRdU LIs and all the clinicopathological parameters were entered simultaneously into the Cox model, BrdU LIs, peritoneal dissemination and serosal invasion emerged as independent prognostic parameters. These results indicate that the in vitro BrdU labelling method using biopsied materials may be useful in predicting lymph node metastasis preoperatively and designing operative procedures for individual patients.

Bromodeoxyuridine↗

PubMed1991

[Flow cytometric analysis of DNA ploidy pattern in advanced gastric cancer and its relationship with prognosis].

Cell nuclear DNA content was determined by flow cytometric analysis in 270 patients with advanced gastric cancer. Aneuploid DNA content was observed in 150 patients (55.6%). The DNA ploidy pattern was the third significantly prognostic factor behind peritoneal dissemination and liver metastasis in Cox regression multivariate analysis. About the relationship between DNA ploidy pattern and other prognostic factors, peritoneal dissemination and wall invasion ratio of aneuploid were significantly higher than those of diploid (p less than 0.01). Five-year survival rate of diploidy patients was significantly higher than that of aneuploidy patients. In stage I, five-year survival rate of patients with diploid tumor was 83.3% and that of patients with aneuploid tumor was 70.0%. In stage II, that of patients with diploid tumor was 81.3% and that of patients with aneuploid tumor was 66.7%. In stage III, that of patients with diploid tumor was 71.2% and that of patients with aneuploid tumor was 25.1%. In stage IV, that of patients with diploid tumor was 31.6% and that of patients with aneuploid tumor was 2.6%. Furthermore in the curative case, that of patients with diploid tumor was 77.2% and that of patients with aneuploid tumor was 48.2%. Aneuploid case has significantly worse prognosis in curative operation.

Adult↗

PubMed1991

[The surgical results of pancreatoduodenectomy and total pancreatogastrectomy combined with autotransplantation of the distal half of the pancreas for the treatment of advanced gastric cancer located in the lower half of the stomach].

In the last 16 years we employed pancreaticodudenectomy (PD) on 27 patients with cancers of the distal third of the stomach, associated with duodenal invasion, invasion to pancreatic head, or n3 metastasis. More recently, total gastrectomy and total pancreatectomy combined with heterotopic autotransplantation of the distal pancreas (TGTP) was performed in 7 patients with n4 metastases. These cases were compared with 56 patients who underwent subtotal gastrectomy (SG) in the same period. When the survival rates were compared, PD provided better long-term results than SG, especially on the patients with tumors infiltrating into the pancreas head. On the contrary, there was no significant survival advantage in patients with duodenal invasion or n3 metastasis between PD group and SG group. TGPT showed the longest survival for the patients with n4 metastasis. These results indicate that PD is a rational and safe method for the treatment of gastric cancer infiltrating into the pancreas head. In addition, TGTP may be the most radical procedure for the treatment of gastric cancer with n4 metastases.

Duodenum↗

PubMed1991

[Application of anti-p-105 monoclonal antibody to analysis of mode of action of antitumor agents].

For the elucidation of the mode of action of anti-tumor agents, the cell cycle analysis of etoposide and podophyllotoxin was examined by means of the multiparameter flow cytometry using an anti-p-105 monoclonal antibody. The p-105 is one of the proliferation associated nuclear antigens and its expression increases with a cell cycle progression, especially in mitotic phase. Thus, we have applied its anti-monoclonal antibody to the discrimination between M and G2 phases of the gastric cancer cells. The results revealed that etoposide caused a G2 block and retarded an S phase transition, and podophyllotoxin caused both G2 and M phase blocks in the gastric cancer cells. This cell cycle analysis using an anti-p-105 monoclonal antibody would be a useful analysis of the antitumor agents, especially for M phase analysis of human cancer cells because of its rapidity and convenience.

Antibodies, Monoclonal↗

PubMed1990

Parvalbumin-immunoreactive neurons in the rat neostriatum: a light and electron microscopic study.

Parvalbumin (PV)-immunoreactive neurons in rat neostriatum were studied under light and electron microscopes. A small number of neurons in the striatum were immunoreactive for PV (a Ca-binding protein). Most of them were also strongly immunoreactive for glutamate decarboxylase but were negative for NADPH-diaphorase activity. Light microscopic analysis revealed that PV-containing neurons have somata with fusiform or polygonal shape and are medium to large in size. The dendrites were smooth and cylindrical at the proximal portion but were varicose at the distal portion. Thin PV-immunoreactive fibers with large boutons were unevenly distributed in the striatum. Electron microscopy revealed that the somata of PV-immunoreactive neurons had a deeply indented nucleus with a nucleolus and often an intranuclear rod. These are the morphological features reported for interneurons of the striatum. Gap junctions formed between two neighboring PV-immunoreactive dendrites. A total of 175 boutons forming synapses with somata and dendrites of PV-immunoreactive neurons were examined. Of these, 115 were small in diameter (less than 1 micron), contained densely packed round vesicles and formed asymmetrical synapses mainly with dendrites. The other 60 boutons formed symmetrical synapses with somata and dendrites of PV-immunoreactive neurons. Both myelinated and unmyelinated axons with boutons were observed. PV-immunoreactive boutons had a diameter of 0.3-2 microns and contained round or elongated vesicles which were about 35 nm in diameter. The boutons formed symmetrical synapses with postsynaptic targets. Of the 100 PV-immunoreactive boutons, 51 were found on somata and proximal dendrites of medium-sized neurons containing a large, round, centrally located nucleus. The others formed synapses with dendrites of various sizes. It was occasionally observed that varicose dendrites free of spines were contacted by a large number of PV-immunoreactive boutons. The study indicates that, in the striatum, immunocytochemistry for PV selectively stains GABAergic interneurons and that the GABAergic interneurons are incorporated in a feed-forward inhibitory circuit of the striatum.

Animals↗

PubMed1990

A clinicopathologic study on multiple gastric cancers with special reference to distal gastrectomy.

Simultaneous multiple gastric cancer was seen in 49 (5.8%) of 852 resected stomachs. Patients with multiple cancers were older than those with single gastric cancers (P less than 0.01) and the incidence of multiple gastric cancer was significantly higher in male patients than in female patients (P less than 0.05). The incidence rates of multiple carcinomas were 9.6% of early gastric carcinomas and 4.0% of advanced gastric carcinomas. With regard to histologic type, the incidence rate of the differentiated type was 71% and the incidence rate of the undifferentiated type was 29%. In 68 serially resected stomachs, 5 (7.4%) new multiple cancers were detected microscopically, whereas 4 (5.9%) had already been diagnosed grossly. The incidence rate of multiple carcinoma increased to 13.2% by this procedure. The cases that were cut serially showed that most of the multiple cancers were located distally from the F-line presenting the line along which intestinal metaplasia appeared. This study suggests that the surgeon is required to resect the area including the F-line at the time of distal gastrectomy so as not to leave another cancer in the gastric remnant.

Adult↗

PubMed1990

Abrogation by novobiocin of cytotoxicity due to the topoisomerase II inhibitor amsacrine in Chinese hamster cells.

Using cultured V79 Chinese hamster cells, we found that novobiocin (or 2,4-dinitrophenol) can abrogate, almost completely, the cytotoxicity due to the topoisomerase II inhibitor amsacrine (mAMSA). V79 cells were sensitive to mAMSA killing at all stages in the cell cycle but mainly in S phase followed by late G1 phase; however, novo rescued cells of all ages. The properties of two kinds of radiation-sensitive Chinese hamster cells were also examined, i.e., the line of V79 cells that can be rescued by caffeine, designated S-10 (H. Utsumi and M.M. Elkind, Radiat. Res., 96: 348-358, 1983); and Chinese hamster ovary cells (P.A. Jeggo and L.M. Kemp, Mutat. Res., 112: 313-327, 1983) which are also sensitive to other DNA-damaging agents. As is the case for exposure to radiation, after mAMSA treatment caffeine rescued V79/S-10 cells. Although Jeggo's Chinese hamster ovary cells were more responsive to mAMSA, novo still abrogated mAMSA toxicity in the mutant cells as well as in the parental Chinese hamster ovary cells 2,4-Dinitrophenol acted similarly to novo with respect to mAMSA killing, but neither compound reduced the ATP content of V79 cells. We propose that one reason for the rescue from mAMSA killing of at least S-phase cells by novo or 2,4-dinitrophenol is their ability transiently to inhibit replicative DNA synthesis.

2,4-Dinitrophenol↗