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Biomedical subjects

M Koono

Publications and source records attributed to M Koono.

At least 91 records · Page 5Linked to original sources
PubMed1994

Stimulation of TIMP-1 and metalloproteinase production in co-cultures of human tumor cells and human fibroblasts.

The co-cultures of five different human tumor cell lines with human normal fibroblasts significantly stimulated the production of tissue inhibitors of metalloproteinases-1 (TIMP-1) when compared to cultures of individual cells. In the co-culture of T24 human urinary bladder carcinoma cells and CCD18 human fibroblasts, production of both TIMP-1 and metalloproteinases was stimulated, and the stimulatory effects were dependent on the cellular ratio between the fibroblasts and carcinoma cells. On day 6 of culture, collagenase and stromelysin were stimulated at a ratio of CCD18 fibroblasts to T24 cells of 1:0.1, while the maximum TIMP-1 production occurred at a ratio of 1:1. Thus, the cellular ratio in the interaction of carcinoma cells with host fibroblasts affects the production of TIMP-1 and metalloproteinases and hence modulates the balance between them.

Cells, Cultured↗
PubMed1993

TPA-enhanced invasion of Matrigel associated with augmentation of cell motility but not metalloproteinase activity in a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1.

We previously found that the enhanced activity to invade Matrigel upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA) was one of the major properties of a highly metastatic variant (L-10) of a human rectal adenocarcinoma cell line RCM-1. To clarify the mechanism of this enhancement, we examined the effect of TPA on 2 major biological factors involved in tumor cell invasion: cell motility and matrix-degrading metalloproteinase activity. The enhanced invasiveness was inhibited by protein-kinase-C inhibitors. TPA markedly enhanced both haptotactic response to type-IV collagen and motility on tissue-culture glass substrate of L-10 cells in a dose-response manner quite similar to that of TPA-enhanced invasion of Matrigel. On the other hand, TPA showed little enhancement of metalloproteinase production, which was assessed by gelatin- and casein-zymography, and of type-IV collagenolytic activity. Addition of TIMP (tissue inhibitors of metalloproteinase)-I inhibited TPA-enhanced invasion of Matrigel by only up to 13%. Thus, TPA treatment of L-10 cells enhanced invasion of Matrigel in association with augmentation of cell motility but did not enhance metalloproteinase activity.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

Enhanced expression of a tumor-cell-derived collagenase-stimulatory factor in urothelial carcinoma: its usefulness as a tumor marker for bladder cancers.

A mouse monoclonal antibody (MAb) E11F4, previously raised against the tumor-cell-derived collagenase-stimulatory factor (TCSF) from LX-1 human lung-carcinoma cells, has been used to define the expression and distribution of TCSF in human non-neoplastic urothelium and tumors of the urinary bladder. Immunohistochemically, TCSF was detected in 27/28 transitional-cell carcinomas (TCC) of the bladder, of which 23 were judged to be positive for TCSF according to objective criteria. Twenty-four of 28 non-neoplastic urothelium from 22 individuals were judged to be negative for TCSF by this criteria. However, TCSF immunostaining that was confined to the superficial umbrella cells was frequently observed in non-neoplastic urothelium. In bladder carcinomas, TCSF was in most cases demonstrated in the majority of cells, including at the invasion front. Its localization to the cell membrane was demonstrated by immunoelectron microscopy. The high level of expression of TCSF in bladder tumors, but not in non-neoplastic urothelium, was also demonstrated by immunoblotting of tissue extracts. Furthermore, E11F4 immunostaining identified tumor cells obtained from bladder washings or voided urine and detected more TCC cases than conventional cytology. Since TCSF immunostaining was positive even in low-grade TCC (immunohistochemically and immunocytochemically in 4/5 TCC grade I), the application of TCSF immunostaining to urine cytology appears promising as a valuable adjunct to conventional methods in the clinical evaluation of patients with TCC.

Antigens, CD↗
PubMed1993

Properties of alpha 1-antitrypsin secreted by human adenocarcinoma cell lines.

alpha 1-Antitrypsin; (alpha 1-AT) produced by various human carcinoma (non-hepatoma) cell lines were analyzed. Five out of eight cell lines secreted detectable amounts of alpha 1-AT into the conditioned media. All were adenocarcinoma cell lines. The tumor cell-derived alpha 1-ATs had higher molecular weights (MW) than the normal plasma form. Most of this difference was an overall reflection of altered N-glycosylation. As judged by binding of lectins, the glycosylation had shifted towards higher levels of triantennary oligosaccharides and higher levels of fucosylation. The conditioned media also contained lower MW alpha 1-AT species, possibly, proteolytically cleaved forms.

Adenocarcinoma↗
PubMed1993

Establishment and characterization of a human lung adenocarcinoma cell line (LC-2/ad) producing alpha 1-antitrypsin in vitro.

A new human cell line, LC-2/ad was established from pleural effusion of pulmonary adenocarcinoma of a 51 year old Japanese female. The LC-2/ad cells exhibit an epithelial appearance and a tendency to form small domes as observed with phase-contrast microscopy. The modal chromosome number was 53-56. Plating efficiency and doubling time were 6.8% and 58 h, respectively (32th passage). Immunocytochemically, the cells were strongly positive for CEA and cytokeratins including cytokeratin no. 18 which is present in simple epithelia. Ultrastructurally, the cultured cells were characterized by well-formed junctional complexes and microvilli. Subcutaneous injection of 5 x 10(6) cells into a nude mouse resulted in tumor formation classified histologically as a moderately differentiated adenocarcinoma. This cell line produced at least two functionally active trypsin inhibitors together with several proteinases in vitro. The main inhibitor was purified partially from the serum-free conditioned medium and confirmed immunologically as human alpha 1-antitrypsin (AAT). Immunohistochemically, the xenografted tumor was also positive for AAT. The cell line LC-2/ad is useful for the study of tumor-derived serine proteinase inhibitors, in particular AAT.

Adenocarcinoma↗
PubMed1993

Autopsy findings in 47 cases of adult T-cell leukemia/lymphoma in Miyazaki prefecture, Japan.

To identify factors that might improve the prognosis of adult T-cell leukemia/lymphoma (ATL), we reviewed data on 47 autopsied cases of ATL with reference to the complications and cause of death. The primary cause of death was respiratory insufficiency due to pulmonary infection. Respiratory insufficiency was also attributed to the diffuse alveolar damage and pulmonary fibrosis resulting from chemotherapy given and oxygen. About 90% of the cases had infections with one or more pathogens. Cytomegalovirus (CMV) was the most frequent pathogen involved in 35/47 (74.5%) while fungal infections were also commonly seen in 25 of the 47 cases (53.2%). Of these, 17 (70%) had pulmonary aspergillosis. Other neoplasias were present in 10 of the 47 cases, while hypercalcemia was evident in 21 patients. These findings suggest that the prevention and treatment of nosocomial infections and of drug-induced pulmonary toxicity may improve the prognosis and quality of life of ATL patients.

Adult↗
PubMed1993

Characteristics of a metastatic variant to the liver of human rectal adenocarcinoma cell line RCM-1.

The interaction of human rectal adenocarcinoma cell line RCM-1 cells with extracellular matrix components, was studied to elucidate the key steps in the liver metastasis of colorectal carcinomas. Highly metastatic variant L-10 cells selected from the metastatic foci of the liver after intrasplenic implantation in nude mice and its parental L-0 cells were used. L-10 cells showed a greater ability to adhere to laminin, fibronectin, and type I and type IV collagens than did L-0 cells but less haptotactic activity than that of L-0 cells to type I or type IV collagen, possibly due to the formation of cellular aggregates. In vitro invasion activities of both cell lines to basement membrane components (Matrigel) or type I collagen were minimal but enhanced by the addition of 12-O-tetradecanoylphorbol-13-acetate (TPA). L-10 cells showed greater ability to invade Matrigel than did L-0 cells, while L-0 cells exhibited higher activity in the invasion of type I collagen than did L-10 cells. TPA did not increase the production of metalloproteinases by both cells when analyzed by gelatin zymography. Based on the differences between the two cell lines, we postulated the following: (1) the high metastatic potential of L-10 cells was due to a greater capacity to attach to and cross the basement membrane; (2) TPA directly enhanced tumor cell invasiveness, not via the increased secretion of metalloproteinases; and (3) haptotactic migration had no significant correlation with the increased metastatic potential of L-10 cells.

Adenocarcinoma↗
PubMed1992

An autopsied case of interferon encephalopathy.

A 78-year-old male with renal carcinoma was treated with a high dose infusion of interferon-alpha (IFN-alpha) for eight months. The patient had evidence of organic brain syndrome such as dysfunction of memory, slowing of behavior, and development of mental confusion that appeared eight months after the treatment. MRI at the time of mental confusion revealed diffuse white matter lesions. Neuropathologic findings were compatible to Binswanger's disease and Senile Dementia of Alzheimer Type (SDAT), Preexisting neurologic abnormalities including intracerebral arteriosclerosis and cerebral atrophy may increase susceptibility to unacceptably severe IFN neurotoxicity.

Aged↗
PubMed1992

An autopsy case report of diffuse esophageal intramural pseudodiverticulosis.

A case report of diffuse esophageal intramural pseudodiverticulosis (EIPD) we encountered at autopsy is described. The pseudodiverticula represented dilated excretory ducts of esophageal submucosal glands with squamous metaplasia of the epithelium. They contained keratin flakes, mucin and/or inflammatory cells which were mainly neutrophils. Submucosal chronic inflammation surrounding the glands was prominent. The findings suggested that the ductal dilatation resulted from obstruction of the ducts by inflammatory material, mucus and desquamated epithelium. To the best of our knowledge, this is the first autopsy report of diffuse EIPD in Japan.

Diverticulum, Esophageal↗
PubMed1992

Pleural malignant fibrous histiocytoma concomitant with pulmonary adenocarcinoma.

A rare autopsy case, in which pleural malignant fibrous histiocytoma (MFH) and peripheral pulmonary adenocarcinoma were present concurrently in the right thorax, is described. Clinically, only a pleural mass was detected because of massive pleural effusion. Since cytologic examination of the effusion showed only adenocarcinoma cells, the pleural mass was considered to be enlarged mediastinal lymph nodes due to metastasis of adenocarcinoma. Histopathologically, the pleural mass showed the features of a common type of MFH, accompanied by metastatic adenocarcinoma cells in the pleural lymphatics. No mixture of MFH and adenocarcinoma cells was present. Immunohistochemically, the MFH lesion showed positive staining for alpha-1-antitrypsin, alpha-1-chymotrypsin, and factor XIIIa, but no reactivity for cytokeratins. The adenocarcinoma lesion showed positive staining for carcinoembryonic antigen (CEA), and contained hyaluronidase-resistant mucin. To our knowledge, this is the second reported case of pleural MFH with pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed1992

Jejunal perforation associated with cytomegalovirus infection in a patient with adult T-cell leukemia-lymphoma.

A patient with adult T-cell leukemia-lymphoma suffered a jejunal perforation, which we believe was directly attributable to cytomegalovirus (CMV) infection. In the areas of ulceration and perforation in the small bowel, blood vessels penetrating the muscularis propria showed extensive lining of cytomegalic endothelial cells with CMV inclusions, accompanied by occasional disruption of the walls, partial occlusion of the lumina, fibrin thrombi, and hemorrhage. The CMV-induced vascular damage seemed to be closely related to the occurrence of ulcers and perforation. The recognition of CMV as a cause of lethal gastrointestinal lesions in immunocompromised hosts has become more important with the advent of anti-CMV therapy.

Adult↗
PubMed1992

Histopathology of eighth cranial nerve of mass stranded dolphins at Goto Islands, Japan.

We examined four dolphins (Grampus griseus) of 582 mass-stranded. Almost no contents were found in the alimentary canal. Nasitrema gondo and Crassicauda grampicola were found in the tympanic cavity. Severe degeneration of the eighth cranial nerve was observed microscopically in all animals and an egg of Nasitrema was found in a tissue crevice of the nerve. We propose that the nerves were damaged directly by Nasitrema.

Animals↗
PubMed1991

Establishment of a new human cancer cell line secreting protease nexin-II/amyloid beta protein precursor derived from squamous-cell carcinoma of lung.

A new cell line (LC-1/sq) of human lung squamous-cell carcinoma was established from a surgically resected specimen of primary lung cancer. Upon continuous propagation in serum-free culture medium, it secreted trypsin inhibitors into the conditioned medium. The major fraction of the trypsin inhibitor (T1-1) was purified to apparent homogeneity by anion-exchange and gel-filtration high-performance liquid chromatography (HPLC) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by transblotting to Immobilon. T1-1 effectively inhibited trypsin. Chymotrypsin, plasmin and kallikrein were inhibited to a lesser extent, but urokinase-type plasminogen activator, elastase, thrombin and papain were not inhibited. The activity of T1-1 was acid-stable and heat-resistant, and its molecular weight was 115 kDa by SDS-PAGE. It exhibited single NH2-terminal sequence, and its first 20 NH2-terminal amino-acid residues were identical with those of protease nexin-II (PN-II)/amyloid beta-protein precursor (APP). These characteristics of T1-1 suggest that the major trypsin inhibitor secreted by LC-1/sq is indistinguishable from PN-II/APP. LC-1/sq is the first lung squamous carcinoma cell line that secretes functionally active trypsin inhibitor, PN-II/APP, in vitro and is useful for studying its biological significance in malignant tumor.

Aged↗
PubMed1991

Glycocalyceal bodies in a human rectal carcinoma cell line and their interstitial collagenolytic activities.

In co-cultivation on a membrane of connective tissue matrix (CTM) obtained from human dura mater, human adenocarcinoma cells (RCM-1) degraded CTM. Morphologically, the destruction of CTM was associated with the shedding of membrane vesicles from the cells. Transmission electron microscopy, using ruthenium red (RR), showed that the shed vesicles were composed of various-sized membrane bound vesicles (MV). A large majority were small glycocalyceal bodies (G-bodies) measuring 20-120 nm in diameter, composed of an amorphous matrix of moderate electron-density surrounded by an RR-positive, trilaminar membrane. G-bodies were separated from medium-sized and large MVs by ultracentrifugation. Ultrastructural observation of the isolated collagen fibrils from CTM co-cultured with RCM-1 cells, showed G-bodies attached to degraded collagen fibrils with characteristic transverse notches along their axes. The lesions occurred as microerosions in the apolar region between the e and d bands of collagen fibrils. Collagenolytic activity in serum-free RCM-1 conditioned medium was localized in the G-body and MV fractions (80% and 20% of the total activity, respectively, when tested against 3H-labeled type I collagen). No activity was detected in the supernatant. The activity in G-bodies was also confirmed by ultrastructural analysis using reconstituted native type I collagen fibrils. The results suggest that RCM-1 cells release interstitial collagenase as a component of G-bodies which facilitates local breakdown of connective tissue during the process of invasion.

Adenocarcinoma↗
PubMed1991

Immunoreactive endothelin in human kidney.

Using a sensitive and specific radioimmunoassay for endothelin, we examined immunoreactive endothelin in human kidney tissue obtained from three necropsy and three nephrectomy cases. Immunoreactive endothelin was present in high concentrations in human kidney inner medulla (necropsy cases: 1.08 +/- 0.47 pg/mg wet weight:mean +/- SE)(nephrectomy cases: 2.77 +/- 0.46). Characterization by reverse phase high performance liquid chromatography indicated that the only immunoreactive endothelin in human kidney inner medulla is endothelin-1, although immunoreactive endothelin in rat and pig kidney inner medulla comprises both isopeptides endothelin-1 and -3, suggesting that the genetic expression of endothelin differs according to species.

Aged↗
PubMed1991

Correlation between urokinase-type plasminogen activator production and the metastatic ability of human rectal cancer cells.

The correlation between the production of plasminogen activators (PA), especially urokinase-type PA (u-PA), by cancer cells and their metastatic potential was studied. For this purpose, cells from the human rectal adenocarcinoma tumor line (RCM-l/nu) originally maintained by serial passage in nude mice as the solid subcutaneous tumor, were injected into the spleen. Cancer cells from liver metastatic foci were suspended and then injected into the spleen. After 10 cycles of this selection, a highly metastatic liver tumor line termed L-10 was obtained. The amount of u-PA in the supernatant of the tumor homogenate of L-10 was larger than that of RCM-l/nu. Using an in vitro culture system, the media conditioned by L-10 cells had a higher PA activity and a higher u-PA antigen level than by RCM-l/nu cells. The apparent difference in u-PA activity and antigen levels of these two lines was not due to the difference in the production of plasminogen activator inhibitor (PAI), because PAI antigen level and PAI activity in the culture media were almost equal between them. No tissue-type PA production was detectable in these tumor lines. From these results we deduce that u-PA may play an important role in tumor metastasis.

Adenocarcinoma↗
PubMed1991

[Clinicopathologic study of adult-onset membranoproliferative glomerulonephritis].

We analyzed clinicopathologic characteristics of adult-onset membranoproliferative glomerulonephritis (MPGN) by comparing two tentatively-classified subgroups. Group A consisted of 9 patients in whom more than 50% of glomeruli showed mixed segmental and global duplication of glomerular basement membrane (GBM), and Group B 9 patients with global duplication of GBM. Group A showed a tendency for more favorable clinical course and outcome than Group B. Nephrotic syndrome was present in 33% of Group A and 100% in Group B, hypertension in 22% and 44%, hypocomplementemia in 44% and 67% at the time of renal biopsy. Deterioration of renal function, at comparable durations of follow-up of 62 +/- 12 (M +/- SE) and 53 +/- 13 months, was observed in 22% of Group A and 56% in Group B, respectively. Histologically, mesangial proliferation and tubulointerstitial change were more pronounced and frequency of sclerosing glomeruli was greater in Group B. There was also a negative correlation between the extent of global double contour and renal function as assessed by creatinine clearance at the time of renal biopsy (r = -0.55, P less than 0.05). These results indicate that the high incidence of global double contour, in addition to the presence of marked tubulointerstitial change and sclerosing glomeruli, may relate to progressive deterioration of renal function in MPGN. That outcomes for Group A and Group B may be different when clinical parameters, including the durations from onset of symptoms to the time of biopsy and length of follow-up periods, are comparable also indicates that these two groups should be considered separate entities, at least on the basis of clinical results.

Adolescent↗