Intralesional steroid injection to prevent stricture after endoscopic submucosal dissection for esophageal cancer: a controlled prospective study.

BACKGROUND AND STUDY AIMS: The frequency of stricture after endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma with a mucosal defect involving more than three-quarters of the circumference is 70% - 90%. Stricture decreases quality of life and requires multiple endoscopic balloon dilation (EBD) sessions. We investigated the efficacy and safety of a single session of intralesional steroid injections to prevent post-ESD stricture. PATIENTS AND METHODS: We conducted a prospective study on 30 patients with esophageal squamous cell carcinoma treated by ESD, who had a more than three-quarter but less than whole circumferential defect. A single session of intralesional steroid injections was undertaken immediately after ESD. Esophagogastroduodenoscopy was performed whenever patients reported dysphagia and 2 months after ESD in patients without dysphagia. Results were compared with a historical control group of 29 patients who underwent ESD without intralesional steroid injection. The primary endpoint was the post-ESD stricture rate. Secondary endpoints were the number of EBD sessions and the complication rate. RESULTS: Compared with the historical control group, the study group had a significantly lower stricture rate (10%, 3/30 patients vs. 66%, 19/29 patients; P < 0.0001) and a lower number of EBD sessions (median 0, range 0 - 2 vs. median 2, range 0 - 15; P < 0.0001). The study group had a complication rate of 7 % (2 /30 patients), comprising a submucosal tear in one patient and bleeding in another, which were not a direct result of EBD. CONCLUSIONS: A single session of intralesional steroid injections showed promising results for the prevention of stricture after ESD for esophageal cancer.

Clinical features and outcomes of delayed perforation after endoscopic submucosal dissection for early gastric cancer.

Perforation is a major complication of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). However, there have been no reports on delayed perforation after ESD for EGC. We aimed to elucidate the incidence and outcomes of delayed perforation after ESD. Clinical courses in 1159 consecutive patients with 1329 EGCs who underwent ESD were investigated. Delayed perforation occurred in six patients (0.45 %). All these patients had complete en bloc resection without intraoperative perforation during ESD. Five of six perforations were located in the upper third of the stomach, while one lesion was found in the middle third. Symptoms of peritoneal irritation with rebound tenderness presented within 24 h after ESD in all cases. One patient did not require surgery because the symptoms were localized, and recovered with conservative antibiotic therapy by nasogastric tube placement. The remaining five patients required emergency surgery. There was no mortality in this case series.

Complications of endoscopic lumbar decompression surgery.

BACKGROUND: Endoscopic lumbar decompression is useful for the treatment of various spinal conditions and is being performed in an increasing number of patients worldwide. We reviewed the surgery-related complications in patients who underwent endoscopic surgery and discuss the learning curve for this procedure. METHODS: Since the first case in August 2000, a total of 138 patients have undergone endoscopic posterior decompression surgery. Of these, there were 74 patients with Herniated Nucleus Pulposus (HNP), 57 with Lumbar Canal Stenosis (LCS), and 7 with other conditions. From 2003 to 2005, the senior surgeon took a sabbatical, and no endoscopic surgery was conducted. We divided the cases based on the date of surgery: there were 62 patients in the early (E) group (before September 2003), and 76 in the late (L) group (from January 2006 to April 2008). We compared the incidence of surgery-related complications between 2 disease types as well as between the E and L groups. RESULTS: We encountered 11 complications, which included 6 dural tears, 2 post-surgical hematomas, 2 neural complications and 1 fracture of the inferior articular process. The incidence of surgery-related complications was 8.6%. The incidences of complications were 8.1% and 9.3% for HNP and LCS, respectively, and 11.3%, and 5.3% in the E and L groups, respectively. The incidence was particularly high (16.7%) in the E group with LCS. CONCLUSION: There is a steep learning curve for endoscopic surgery. Based on the data, surgeons should start performing endoscopic techniques for LCS after gaining enough experience of endoscopic surgery for HNP.

Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme.

The interleukin-1beta (IL-1beta) converting enzyme (ICE) processes the inactive IL-1beta precursor to the proinflammatory cytokine. ICE was also shown to cleave the precursor of interferon-gamma inducing factor (IGIF) at the authentic processing site with high efficiency, thereby activating IGIF and facilitating its export. Lipopolysaccharide-activated ICE-deficient (ICE-/-) Kupffer cells synthesized the IGIF precursor but failed to process it into the active form. Interferon-gamma and IGIF were diminished in the sera of ICE-/- mice exposed to Propionibacterium acnes and lipopolysaccharide. The lack of multiple proinflammatory cytokines in ICE-/- mice may account for their protection from septic shock.

Endoscopic submucosal dissection for early gastric cancer performed by supervised residents: assessment of feasibility and learning curve.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is feasible as a treatment for early gastric cancer (EGC) when it is performed by an experienced endoscopist. We investigated whether it was feasible for novice endoscopists to perform ESD for EGC, and how difficult it was to learn the procedure. METHODS: This case series study was performed in a cancer referral center. Three resident endoscopists, who had already learned basic procedures, performed ESD under supervision for 30 consecutive lesions, and their procedures were analyzed. The procedure was divided for assessment into (i) mucosal incision and (ii) submucosal dissection by completion of the circumferential mucosal cut. An insulated-tip knife was used for mucosal incision and submucosal dissection. A total of 90 mucosal EGCs (< or = 2 cm) without ulcers or scars in 87 patients were included. Outcomes were: rates of complete resection, complications, and self-completion; operation time; learning curve; and reasons for change of supervisor as an indicator of difficulty. RESULTS: Among the 90 procedures, there was a good overall complete resection rate of 93 %, with an acceptable complication rate of 4.4 %; the complications were delayed hemorrhage in two patients, and perforations in another two patients that were repaired successfully by endoscopic clipping. The self-completion rate and operation time were significantly worse for submucosal dissection than for mucosal incision. Two of the three operators showed a flat learning curve for submucosal dissection. Difficulty with the procedure was related mainly to uncontrollable hemorrhage. CONCLUSIONS: With appropriate supervision, gastric ESD by residents is feasible, with equivalent complete resection rates and acceptable complication rates compared with those of experienced endoscopists, although there was difficulty in achieving sufficient self-completion rates in submucosal dissection. Better control of bleeding during submucosal dissection may be a key to improving the procedure.

Bile acid synthesis by long-term cultured cell line established from human hepatoblastoma.

Bile acids in the spent medium for the cell culture were analyzed by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry to determine whether human hepatoblastoma cell line could synthesize bile acids. Cholic, chenodeoxycholic, and lithocolic acids were found in the culture medium, and a portion of chenodeoxycholic acid and all of lithocholic acid were sulfated. Since the cells had been cultured in serum-free medium, it is clear that the bile acids were newly synthesized and sulfated by the cultured cells. Chenodeoxycholic acid was the main bile acid in the medium, suggesting that the cell line might predominantly synthesize chenodeoxycholic acid. On the other hand, the cells had fetal or hepatoma characters such as marked alpha-fetoprotein production. These results suggest that fetal or hepatoma type bile acid metabolism might occur in the cell line, and that the established cell line could be an useful in vitro model for the study of bile acid metabolism in hepatoma.

Serum pseudouridine as a biochemical marker in small cell lung cancer.

The serum level of pseudouridine, primarily a degradation product of tRNA, was determined by high-performance liquid chromatography in 24 patients with small cell lung cancer (SCLC), 13 patients with non-SCLC with advanced stages, 15 patients with pulmonary infectious diseases, and 18 healthy controls. The mean serum pseudouridine concentration was significantly higher in the patients with SCLC [4.75 +/- 1.76 (SD) nmol/ml] than that in the patients with pulmonary infectious diseases (3.39 +/- 1.38 nmol/ml) or in healthy controls (2.21 +/- 0.78 nmol/ml). The mean serum pseudouridine concentration in the patients with non-SCLC (4.07 +/- 0.95 nmol/ml) was significantly higher than that in healthy controls but not statistically different from that in the patients with pulmonary infectious diseases. The serum pseudouridine level was elevated above the mean value plus 2 SD for the healthy subjects (3.77 nmol/ml) in 66.7% of all patients with SCLC including 3 of 8 (37.5%) with limited disease and 13 of 16 (81.3%) with extensive disease, and 53.8% of the patients with non-SCLC. Serum carcinoembryonic antigen was elevated (greater than 5 ng/ml) in 29.2% and serum neuron-specific enolase (greater than 10 ng/ml) in 58.3% of the cases with SCLC. In the patients with SCLC followed up during chemotherapy, serum pseudouridine levels changed considerably parallel with the changes in the clinical response. These findings indicate that serum pseudouridine may be a useful biochemical marker in the patients with SCLC.

Expression of a hybrid form of alkaline phosphatase isoenzyme in a newly established cell line (HuG-1) from a gastric cancer patient.

An unusual alkaline phosphatase (AP), named HuG-AP, was found in a newly established cell line (HuG-1) derived from a patient with stomach cancer. The enzyme was purified about 300-fold by affinity chromatography. On polyacrylamide gradient (4-30%) gel electrophoresis, the one band with the enzyme activity was observed. The enzymic properties of HuG-AP did not conform to those of liver, intestinal, placental, and germ cell AP isoenzymes which were recognized as homodimeric structure. Thermostability of the HuG-AP showed an intermediate value between intestinal and placental APs. Immunologically, the HuG-AP reacted with both anti-intestinal and anti-placental AP monoclonal antibodies. Dot blot analysis showed that both intestinal and placental AP mRNAs were expressed in HuG-1 cells concurrently. Therefore, we concluded that this novel AP had a hybrid form, namely heterodimeric structure, consisting of one subunit each of intestinal and placental APs. However, all of the properties of this hybrid AP did not conform to the intermediate enzymic properties between intestinal and placental APs which would be shown when they both coexist. Because an AP identical to HuG-AP had already been found in the metastatic lesion of the liver of the same patient, the expression of this novel AP seemed to occur in the patient's original cancer cells but did not result from spontaneous transformation of cultured cells.

Structures of the asparagine-linked oligosaccharides of an alkaline phosphatase, kasahara isozyme, purified from FL amnion cells.

Asparagine-linked oligosaccharides were quantitatively released by hydrazinolysis from an alkaline phosphatase, Kasahara isozyme, which was purified from FL amnion cells. Almost all of the oligosaccharides (98%) were acidic components, all of which can be converted to neutral oligosaccharides upon sialidase digestion. Structural analysis of the oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis revealed that the alkaline phosphatase of FL cells contains sialylated mono-, bi-, tri-, and tetraantennary complex type sugar chains with the Gal beta 1----4GlcNAc beta 1---- outer chains. Some of the tetraantennary sugar chains contain a single Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- outer chain on their Man alpha 1----6 arm. Both fucosylated and nonfucosylated trimannosyl cores were found in the sugar chains. However, it is of interest that the core portion of monoantennary oligosaccharide was not fucosylated and that of the tetraantennary oligosaccharide with a tetrasaccharide outer chain was completely fucosylated.

Increase of fucosylated serum cholinesterase in relation to high risk groups for hepatocellular carcinomas.

Serum cholinesterase (ChE) (E.C. 3.1.1.8) is a glycoprotein which has 36 potential sites of asparagine-N-linked sugar chains. The structures of oligosaccharides released from ChE on hydrazinolysis were studied by serial lectin affinity column chromatography, exoglycosidase digestion, and methylation analysis. Seventy-three % of the sugar chains occurred as biantennary oligosaccharides and the remainder as C-2 and C-2,4/C-2,6 branched tri- and tetraantennary oligosaccharides. Several percentages of the Lewis X antigenic determinant and fucosylated mannose core were linked to them, and their sialic acid residues were linked to nonreducing terminal galactose residues at the C-3 and C-6 positions. Aleuria aurantia lectin-reactive ChE with the Lewis X antigenic determinant increased in hepatocellular carcinomas and liver cirrhosis compared with chronic hepatitis; on the other hand, Aleuria aurantia lectin-reactive ChE did not change significantly after transcatheter arterial embolization and was not related to the serum levels of alpha-fetoprotein and carcinoembryonic antigen in patients with hepatocellular carcinomas. Accordingly, the analysis of Aleuria aurantia lectin-reactive ChE is clinically useful for differentiating liver cirrhosis from chronic hepatitis and to identify high risk groups for hepatocellular carcinomas, i.e., cirrhotic patients in Child's A grade.

Characterization of an established cell line from human renal carcinoma.

A cell line, designated as OUR-10, has been established from a renal carcinoma in a Japanese woman. This cell line forms monolayers of polygonal epithelial cells with scattered round or dendritic cells and exhibits multilayering. With electron microscopy, differentiated surface structures that resemble the microvilli characteristic of renal carcinomas can be seen even at the 60th transfer. The cells have a hypodiploid karyotype with modal numbers of 39 and 40. No marker chromosomes were seen, but definite nonrandom loss of three chromosomes in Group D and one in Group E were recognized. The doubling time was estimated as approximately 32 hr in exponentially growing cultures, and the cells formed colonies in soft agar with an average efficiency of 25%. Heterotransplantation into the cheek pouch of immunosuppressed hamsters produced tumors that were histologically similar to the original cancerous tissue. The electrophoretic mobility of gamma-glutamyl transpeptidase extracted from the cells coincided with that of a novel isozyme found in human renal carcinoma tissue, and the genetic phenotype of the glucose-6-phosphate dehydrogenase was proved to be the B phenotype. The antigenic structure of HLA was determined as HLA-A2, 11; B5, 40, which was the same as that of peripheral blood lymphocytes of the woman with renal carcinoma.

Alteration of hexosaminidase isozymes in human renal carcinoma.

The activity and isozyme patterns of hexosaminidase in human renal carcinoma were studied in comparison with those of normal kidney. Hexosaminidase in extracts from normal kidney and renal carcinoma tissue could be separated into two major forms [hexosaminidase A (Hex A) and hexosaminidase B (Hex B)] by Cellogel electrophoresis or by diethylaminoethyl cellulose column chromatography. All of 10 renal carcinoma tissues showed a low activity ratio of Hex A to Hex B, as compared with the ratio in normal kidney; the ratio in renal carcinoma tissue was between 0.61 and 2.21 (mean, 1.30), while that in normal kidney was between 2.50 and 4.52 (mean, 3.46). Hexosaminidase activity and the ratio of Hex A to Hex B in renal carcinoma tissue were independent of the cell type and the differentiation grade of carcinoma tissue. Hex A and Hex B of renal carcinoma tissue differed from each other in physicochemical properties such as pH dependence of enzyme activity, thermostability, and Km's for two synthetic substrates, but each isozyme maintained its same physicochemical properties whether from normal or from carcinoma tissue. The isozyme patterns of cultured renal carcinoma cells and placenta were similar to those of the carcinoma tissue. The results presented here indicate that hexosaminidase isozymes in renal carcinoma tissue express at least oncoplacental patterns.

CT-based morphological assessment of the hip joint in Japanese patients: association with radiographic predictors of femoroacetabular impingement.

AIMS: Femoroacetabular impingement (FAI) has been highlighted and well documented primarily in Western countries and there are few large studies focused on FAI-related morphological assessment in Asian patients. We chose to investigate this subject. PATIENTS AND METHODS: We assessed the morphology of the hip and the prevalence of radiographic FAI in Japanese patients by measuring predictors of FAI. We reviewed a total of 1178 hips in 695 men and 483 women with a mean age of 58.2 years (20 to 89) using CT images that had been obtained for reasons unrelated to symptoms from the hip. We measured the lateral centre edge angle, acetabular index, crossover sign, alpha angle and anterior femoral head-neck offset ratio. RESULTS: A total of 441 hips (37.4%) had pincer-type deformity (41.7% men, 31.3% women) and 534 (45.3%) had cam-type deformity (54.4% men, 32.3% women). Moreover, 773 hips (65.6%) had at least one parameter that predisposes to FAI (74.0% men, 53.6% women) and 424 hips (36.0%) had two or more parameters (43.6% men, 25.0% women). CONCLUSION: The prevalence of radiographic FAI was common in Japanese patients who are generally considered to have dysplastic hips. Cite this article: Bone Joint J 2016;98-B:1167-74.

Purification and properties of 3 alpha-hydroxysteroid dehydrogenase as a 3-keto bile acid reductase from human liver cytosol.

The NADPH-dependent 3 alpha-hydroxysteroid dehydrogenases (peaks 1, 2 and 3) acting on 3-keto-5 beta-cholanoic acid separated by carboxymethyl-cellulose chromatography from human liver cytosol were purified to homogeneous protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, using Affi-Gel blue, phenyl-Sepharose CL-4B, TSKgel G3000 SW chromatography and chromatofocusing. The overall purifications of the enzymes from cytosol were 316-fold (peak 1), 232-fold (peak 2) and 345-fold (peak 3) and the recoveries of the enzymes were 0.4% (peak 1), 7.1% (peak 2) and 3.7% (peak 3). The isoelectric points of the enzymes were found to be 7.34, 7.46 and 7.88 by chromatofocusing. The molecular weights of the enzymes were similar and estimated to be about 32,000 by size exclusion chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzymological properties were nearly identical among the three forms. The reaction was reversible and the optimum pH of the enzymes for oxidation was about 8.4 and that for reduction was about 7.4. The enzymes could not reduce 7 alpha,12 alpha-dihydroxy-3-keto-5 beta-cholanoic acid, 7 alpha-hydroxy-5 beta-cholestan-3-one and 7 alpha, 12 alpha-dihydroxy-5 beta-cholestan-3-one to the corresponding 3 alpha-hydroxysteroids, whereas the enzymes could reduce 3,7-disubstituted 3-keto bile acids. Thus, the enzymes purified in this study were found to have a stereospecific character for some 3-ketosteroids. The enzyme activity was inhibited by p-chloromercuribenzoate; however, the inhibition was prevented by addition of dithiothreitol to the reaction mixture, indicating that the enzyme required a sulfhydryl group for activity.

A newly discovered apolipoprotein B-containing high-density lipoprotein produced by human hepatoma cells.

Apolipoprotein B-containing high-density lipoprotein was detected in the high-density lipoprotein fraction of the concentrated conditioned medium of human hepatoma HuH-7 cells (Apo-B-containing HDLHuH-7). Electrophoretically, the Apo-B-containing HDLHuH-7 migrated more slowly and broadly than beta-lipoprotein on agarose gel. The Apo-B-containing HDLHuH-7 was not precipitated by heparin-Mn2+ treatment. High-performance gel filtration chromatography indicated that the peak of Apo-B-containing HDLHuH-7 was eluted faster than that of plasma LDL and electron microscopic analysis demonstrated that the particles of Apo-B-containing HDLHuH-7 ranged from 140 A to about 450 A, indicating the heterogeneity of Apo-B-containing HDLHuH-7. The protein/lipid ratio of HDLHuH-7 (1.35) is higher than that of plasma HDL3 (1.2). The lipids of HDLHuH-7 are composed of phospholipids (170 micrograms/mg protein), free cholesterol (410 micrograms/mg protein), cholesterol ester (20 micrograms/mg protein) and triacylglycerols (140 micrograms/mg protein). The results described above indicated that Apo-B-containing HDLHuH-7 was a novel lipoprotein discovered for the first time.

Partial purification and characterization of 7 alpha-hydroxysteroid dehydrogenase from rat liver microsomes.

An NADPH-dependent 7 alpha-hydroxysteroid dehydrogenase acting on 3 alpha-hydroxy-7-keto-5 beta-cholanoic acid was partially purified 160-fold with a yield of 13% from rat liver microsomes using DEAE-cellulose, hydroxyapatite and Affi-Gel Blue column chromatography. The specific activity of the purified enzyme was 91.3 nmol chenodeoxycholic acid formed/min per mg of protein. The reaction was reversible, and the optimum pH of the enzyme for the oxidation was about 8.5, whereas that for the reduction was about 5.0 A molecular weight of the enzyme was estimated to be about 130,000 by Superose 6TM gel filtration chromatography. The apparent Km value for 3 alpha-hydroxy-7-keto-5 beta-cholanoic acid was 35.7 microM and that for NADPH was 90.9 microM. The preferred substrate for the enzyme was 3 alpha-hydroxy-7-keto-5 beta-cholanoic acid rather than 3 alpha,12 alpha-dihydroxy-7-keto-5 beta-cholanoic acid, a 7-keto-bile acid analogue. The enzyme also preferred the unconjugated form to the conjugated forms. The enzyme activity was inhibited by p-chloromercuribenzoate; however, the inhibition was prevented by addition of reduced form of glutathione to the reaction mixture, indicating that the enzyme requires a sulfhydryl group for activity.

Effect of interferon-gamma on purine catabolic and salvage enzyme activities in rats.

To determine whether interferon-gamma affects rat purine catabolic and salvage enzyme activities, rats were injected with interferon-gamma (600000 U/kg, i.p.) and, similarly to a vehicle-injected control group, killed before or after injection at 6, 12, and 24 h. Organ homogenates were prepared and enzymatic reactions with substrates were carried out, after which the products were measured either chromatographically or spectrophotometrically. Western and Northern blotting also were performed. In contrast to the vehicle-injected rats, interferon-gamma-injected rats showed a significant rise in xanthine oxidoreductase activity in the liver, while enzyme activity was unchanged in the spleen, kidney, and lung. Western analysis of hepatic xanthine oxidoreductase showed an increased concentration of this protein 12 and 24 h after interferon-gamma injection. Northern analysis disclosed an enhanced mRNA expression coding for this enzyme, peaking 12 h after injection. Contrastingly, the activities of adenosine deaminase, purine nucleoside phosphorylase, hypoxanthine guanine phosphoribosyltransferase, and adenine phosphoribosyltransferase were not affected by interferon-gamma in any organ tested. While interferon-gamma causes an increased hepatic biosynthesis of xanthine oxidoreductase, the physiologic role of this enzyme induction remains undetermined.

Reduction of 3-keto-5 beta-cholanoic acid to lithocholic and isolithocholic acids by human liver cytosol in vitro.

The formation of lithocholic and isolithocholic acids from 3-keto-5 beta-cholanoic acid by human liver cytosol was examined in vitro. Liver cytosol was incubated at various pH levels with 3-keto-5 beta-cholanoic acid in a phosphate buffer containing NADPH or NADH; the products formed were analyzed by gas chromatography. Results showed that human liver cytosol reduced 3-keto-5 beta-cholanoic acid to lithocholic acid at a pH level of 7.0 or above and to isolithocholic acid at a pH level of 6.0 or below when NADPH was used as a coenzyme, and it was reduced to isolithocholic acid only when NADH was used. Furthermore, two peaks for the reducing enzymes could be clearly found by column chromatography of Affi-Gel Blue. These results indicate that human liver cytosol contains two enzymes acting on reduction of 3-keto-5 beta-cholanoic acid to lithocholic and isolithocholic acids, which are dependent on the pH level and the use of NADPH or NADH in vitro. Since the 3 beta-dehydrogenation was inhibited by the addition of pyrazole, an alcohol dehydrogenase inhibitor or ethanol, and the major peak of 3 beta-hydroxysteroid dehydrogenase coincided with the peak of alcohol dehydrogenase on Affi-Gel Blue chromatography, at least some of the cytosolic 3 beta-hydroxysteroid dehydrogenase seemed to be identical to or to have characteristics similar to alcohol dehydrogenase.

Novel apoprotein A-I-containing lipoprotein produced by a human hepatoma-derived cell line HuH-7.

The apoprotein A-I (apo A-I)-containing lipoprotein (LPHuH-7apoA-I) was isolated from the concentrated conditioned medium of human hepatoma-derived cell line HuH-7 by immunoaffinity chromatography. LpHuH-7apoA-I consists of two kinds of lipoproteins. One is a lipoprotein of large particle size (LpL) with broad electrophoretic mobility on agarose gel ranging from the origin to the position of prebeta-lipoprotein. LpL is protein-rich in composition (protein, 75.4% by weight) and is heterogeneous in size (34-17 nm in diameter) electron microscopically. However, the most intriguing properties of LpL are its partial electrophoretic mobility towards the cathode on agar gel. The other lipoprotein is of small particle size (LpS). It demonstrates prebeta-electrophoretic mobility on agarose gel. LpS is also protein-rich in composition (protein, 95.4% by weight) and is heterogeneous in size (16.5-8.4 nm in diameter) electron microscopically. LpL is obviously different from LP-X and LP-Y in property, although LP-X, LP-Y and a part of LpL migrate towards the cathode on agar gel electrophoresis. LpS is also different from human apo A-I-containing lipoprotein without apo A-II in property, although these two lipoproteins possess the same mobility on agarose gel electrophoresis. These results indicate that both LpL and LpS are novel lipoproteins which have not yet been reported. The major isoproteins of the apo A-I of LpHuH-7apoA-I are apo A-I isoprotein 2 (apo A-I2), apo A-I isoprotein 4 (apo A-I4) and apo A-I isoprotein 5 (apo A-I5), and are different from those of apo A-I in human plasma and in the conditioned medium of hepatoma-derived cell line HepG2. This result suggests the presence of a proteinase which converts proapoprotein A-I (apo A-I2) to apoprotein A-I (apo A-I4) in the conditioned medium of HuH-7.