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Biomedical subjects

M Koono

Publications and source records attributed to M Koono.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

[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

Prognostic significance of alpha-1-antitrypsin in early stage of colorectal carcinomas.

We have previously shown that human colorectal carcinoma cell lines, RCM-1 and CoCM-1, synthesize alpha-1-antitrypsin (alpha 1-AT) in culture. We have studied immunohistochemically the incidence of alpha 1-AT on histologic sections from paraffin-embedded tissues of surgically resected colorectal carcinomas and their metastatic foci, polypectomized adenomas, and normal mucosae. alpha 1-AT was detected in 89 (61%) of 145 carcinomas (including 14 carcinomas in adenoma), and 12 (39%) of 31 adenomas. But only 2 (4%) of 55 normal colorectal mucosae were positive for alpha 1-AT. In metastatic tumor cells of colorectal carcinomas in lymph nodes and other organs, alpha 1-AT positivity was 60% and 82%, respectively. The incidence of alpha 1-AT was markedly higher in advanced adenocarcinomas than in early ones and more frequent in adenocarcinomas of right side (including transverse colon) than those of left side and rectum, regardless of their histological malignancy grades. In mucinous carcinomas the frequency was greater (8 of 9 cases) than in conventional adenocarcinomas. Clinical follow-up of the patients with colorectal carcinomas suggested that alpha 1-AT positivity in Dukes' stage A/B tends to correlate with unfavorable prognosis irrespective of the grade of histologic differentiation of carcinoma, but there is no significant relation in Dukes' stage C/D. Our findings suggest that alpha 1-AT in colorectal carcinoma is related to the invasive and metastatic capacity. It may thus serve as a biologic marker for prognosis of colorectal carcinomas at relatively early stages (Dukes' stage A/B).

Adenoma

Truncus solitarius pulmonalis.

The case of a female neonate with truncus solitarius pulmonalis (TSP), a rare congenital heart anomaly, is reported. She died four days after birth. A single right ventricle with common atrioventricular (AV) valve was associated with (Collet & Edwards type II) truncus arteriosus communis, and appeared to have a single coronary artery with an abnormally high take-off near the origin of the right subclavian artery. However, the vessel that appeared to be the single coronary artery was in fact an extremely hypoplastic ascending aorta associated with aortic atresia and agenesis of the left ventricle and mitral valve.

Coronary Vessel Anomalies

[Renal failure associated with polyarteritis nodosa].

We reported 5 patients with renal failure associated with polyarteritis nodosa (PN). In all patients the renal dysfunction became apparent from 2 to 4 weeks after the onset of fever or neuromuscular symptoms with laboratory findings supporting marked inflammatory process and took the course of either acute or rapidly progressive renal failure. The clinical diagnoses on admission were variable; fever of unknown origin, peptic ulcer disease, polyneuritis multiplex, disseminated intravascular coagulation and Buerger's disease. Microscopic examination of the kidneys in 3 by renal biopsy and in 2 by autopsy revealed crescentic glomerulonephritis without immunoglobulin deposit, segmental necrotizing glomerulonephritis, marked inflammatory infiltrate around the glomeruli, granulomatous lesion, tubular necrosis and cortical necrosis other than necrotizing vasculitis. The outcomes were favorable with prednisolone monotherapy in two patients who had biopsy-proven diagnosis and treatment early in the course. Of all PN the prevalence of renal involvement is considered to be about 70%, the prognosis of which has been considered very poor. However it seems possible to alter fatal outcome of this disease by starting treatment with confident histological proof early in the disease process.

Acute Kidney Injury

New human colorectal carcinoma cell lines that secrete proteinase inhibitors in vitro.

Two new human cell lines, RCM-1 and CoCM-1, have been established from primary colorectal adenocarcinomas. Both cell lines were unique in that the cultures secreted trypsin inhibitors in vitro. The activities of these inhibitors were accumulated in serum-free media of both cell lines over a period of several days. Two inhibitors (PI-1 and PI-2) were isolated from serum-free conditioned medium in which RCM-1 was grown by anion-exchange and gel filtration high-performance liquid chromatography. PI-1 inhibited trypsin and chymotrypsin strongly, and pancreatic elastase weakly. Its molecular weight was about 57 kilodaltons (Kd) as determined by gel filtration chromatography. It cross-reacted with the antiserum elicited against human alpha 1-antitrypsin in double immunodiffusion. PI-1 corresponding to alpha 1-antitrypsin was also demonstrated immunohistochemically in both cell lines. PI-2 inhibited trypsin strongly, and chymotrypsin, kallikrein and plasmin weakly. It had higher molecular weight (200-300 Kd) than that of PI-1, and did not cross-react with antisera against human alpha 1-antitrypsin, alpha 2-macroglobulin, alpha 1-antichymotrypsin, alpha 2-plasmin inhibitor, inter-alpha-trypsin inhibitor and urinary trypsin inhibitor. RCM-1 and CoCM-1 are the first colorectal adenocarcinoma cell lines that secrete functionally active trypsin inhibitors, including alpha 1-antitrypsin in vitro, and are useful for the study of tumor-cell derived proteinase inhibitors.

Adenocarcinoma

Neutral proteinases and inhibitors secreted by human rectal adenocarcinoma cell line (RCM-1).

A human rectal adenocarcinoma cell line, RCM-1, secreted some neutral proteinases: metallo-, serine and cysteine proteinases; and trypsin inhibitors into the serum-free conditioned medium (SFCM) in vitro. They were separated by anion-exchange and gel filtration high-performance liquid chromatography. SFCM from the cells of early passage numbers (20-24) contained native activities of serine proteinase and collagenolytic metalloproteinase. However, after several passages the native activities of them were diminished and latent form of metalloproteinase increased. In contrast to the native proteolytic activities, trypsin inhibitory activity was elevated in SFCM from the cells of passages 38-42. It inhibited the serine proteinase secreted by the same cells of early passage numbers. Furthermore, the serine proteinase was able to activate the latent form of metalloproteinase. Cooperative roles of these tumor-secreted proteinases and inhibitors may be important in tumor invasion.

Adenocarcinoma

High-molecular-weight neutral proteinase of rat ascites hepatoma cells and their collagenolytic activity.

A high-molecular-weight proteinase in rat ascites hepatoma AH109A cells was purified to apparent homogeneity by conventional chromatographic techniques. The purified proteinase degraded over the broad pH range, 7.0-9.0, not only denatured hemoglobin but also type I and IV collagen in the absence of calcium. Its activity was maximum at pH 8.0, heat-labile and affected by thiol reagents. Serine proteinase inhibitors such as diisopropyl fluorophosphate, soybean trypsin inhibitor, leupeptin, and antipain also partially inhibited its activity. The enzyme was found mainly in the cytosol fraction, and had a molecular weight of 450 kilodaltons (Kd) as determined by gel filtration chromatography and showed a single band on polyacrylamide gel electrophoresis under nondenaturing condition, although it was dissociated into lower-molecular-weight subunits, 25.5-32 Kd in the presence of sodium dodecyl sulfate and 2-mercaptoethanol. These properties suggested that it was a kind of a cytosolic high-molecular-weight proteinase. The collagenolytic activity of this proteinase may play an important role in cancer cell invasion and metastasis.

Animals

A new long-term in vitro invasion assay using fibrous connective tissue matrices maintaining architectural characteristics of connective tissue.

A long-term invasion assay using fibrous connective tissue matrices was developed. The matrices were prepared by treating murine skin or human dura mater with 25 mM ammonium hydroxide containing proteinase inhibitors at 4 degrees C for 7 days. They could be maintained almost indefinitely without the degeneration and necrosis. Electron micrographs of them revealed the preservation of native collagen fibers, and sequential enzyme digestion showed the presence of glycoprotein in the matrices. Local dissolution of extracellular matrix by cultured human rectal adenocarcinoma cell line, RCM-1, was observed morphologically and confirmed by a quantitative assay using radiolabeled matrices. The destruction of extracellular matrix occurred associated with membrane vesicle-shedding from the cells. Both the advantages and disadvantages of this assay were discussed.

Animals