Biomedical subjects

Y Hori

Publications and source records attributed to Y Hori.

At least 73 records · Page 4Linked to original sources

PubMed2000

FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development.

FGF receptor 2 isoform IIIb (FGFR2b), originally discovered as a receptor for FGF7, is known to be an important receptor in vertebrate morphogenesis, because FGFR2b null mice exhibit agenesis or dysgenesis of various organs, which undergo budding and branching morphogenesis. Since FGF7 null mice do not exhibit marked defects in organogenesis, it has been considered that other FGF(s) than FGF7 might function as a major ligand for FGFR2b during organogenesis. One of the candidate ligands is FGF10, because FGF10 binds to FGFR2b with high affinity and the formation of the limb and lung is arrested in FGF10 null mice as found in FGFR2b-deficient mice. Previous analyses of FGF10 null mice revealed that FGF10 is required for limb and lung development. To elucidate the role of FGF10 in wide-range organogenesis, we further analyzed the phenotypes of the FGF10 knockout mice. We found diverse phenotypes closely related to those for FGFR2b-deficient mice, which includes the absence of thyroid, pituitary, and salivary glands, while minor defects were observed in the formation of teeth, kidneys, hair follicles, and digestive organs. These results suggest that FGF10 acts as a major ligand for FGFR2b in mouse multi-organ development.

Animals↗

PubMed2000

A staining procedure for micronucleus test using new methylene blue and acridine orange: specimens that are supravitally stained with possible long-term storage.

The micronucleus test has been widely used as an in vivo cytogenetic test. It employs two different kinds of supravital staining methods which use either new methylene blue (N) and Giemsa (G) or acridine orange (AO). We have developed a new staining procedure for the preparation of specimens supravitally stained with possible long-term storage, using both N and AO. This N/AO-staining method involves three steps; (1) combination of the target tissue or target cells with an equivalent volume of 0.5% solution of new methylene blue (N-staining step), (2) immediate smear of the mixture, followed by treatment with methanol for 10 min for fixation and removal of N and drying (referred to as fixed-decolorized specimens), and (3) staining with 0.007% solution of AO for 3 min, followed by washing with Sörensen's buffer (pH 6.8) and covering of specimens before observation (AO-staining step). To examine whether the N/AO-staining method is useful for the micronucleus test, comparisons were made between N-, N/AO-, and AO-stained specimens prepared supravitally from peripheral blood of rats with and without treatment of cyclophosphamide. The results indicate that N/AO-stained specimens can be supravitally observed after long-term storage with the same coloration and comparable frequencies of micronucleated reticulocytes with a positive response as AO-stained specimens, if the staining process is temporarily stopped before AO-staining (as fixed-decolorized specimens), or if the AO-staining step is repeated. The results also showed that separated reticulocyte types are supravitally stained in a similar fashion to N-stained specimens but not to AO-stained specimens, indicative of the preservation of the supravital feature of N-staining. Taken together these results suggest that the N/AO-staining procedure could offer an additional useful staining tool for the micronucleus test.

Acridine Orange↗

PubMed2000

Effects of the second-generation leukotriene B(4) receptor antagonist, LY293111Na, on leukocyte infiltration and collagen-induced arthritis in mice.

The effects of the second-generation leukotriene B(4) receptor (LTB(4) receptor) antagonist, 2-[2-propyl-3-¿3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxy-phenoxy]-propo xy¿phenoxy]benzoic acid sodium salt (LY293111Na), on leukotriene B(4)-induced leukocyte infiltration and interleukin-1-accelerated collagen-induced arthritis in mice were studied. Neutrophil infiltration induced into an air pouch by leukotriene B(4) was dose-dependently inhibited by LY293111Na and strongly so by another LTB(4) receptor antagonist, 4-[5-¿4-(aminoiminomethyl)phenoxy¿pentoxy]-3-methoxy-N, N-bis(1-methylethyl) (Z)-2butenedioate (1:1) (CGS25019C). Both compounds significantly inhibited the increase of the arthritis index and the ankle bone destruction in interleukin-1-accelerated collagen-induced arthritis. Phenidone, a 5-lipoxygenase inhibitor, also inhibited interleukin-1-accelerated collagen-induced arthritis, while indomethacin and tenidap, cyclooxygenase inhibitors, had slight inhibitory effects. Injection of interleukin-1 elicited a marked increase of the leukotriene B(4) level in arthritic paws, while the prostaglandin E(2) level was slightly increased. These findings indicate clearly that leukotriene B(4) is an important mediator of interleukin-1-accelerated collagen-induced arthritis in mice. If this can be extrapolated to man, LTB(4) receptor antagonists might be useful for treatment of the acute progressive phase of human arthritis.

Animals↗

PubMed2000

Novel antiarthritic agents with 1,2-isothiazolidine-1,1-dioxide (gamma-sultam) skeleton: cytokine suppressive dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase.

Various 1,2-isothiazolidine-1,1-dioxide (gamma-sultam) derivatives containing an antioxidant moiety, 2,6-di-tert-butylphenol substituent, were prepared. Some compounds, which have a lower alkyl group at the 2-position of the gamma-sultam skeleton, showed potent inhibitory effects on both cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO), as well as production of interleukin (IL)-1 in in vitro assays. They also proved to be effective in several animal arthritic models without any ulcerogenic activities. Among these compounds, (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1, 2-isothiazolidine-1,1-dioxide (S-2474) was selected as an antiarthritic drug candidate and is now under clinical trials. The structure-activity relationships (SAR) examined and some pharmacological evaluations are described.

Animals↗

PubMed2000

The catalytic RNA of RNase P from Escherichia coli cleaves Drosophila 2S ribosomal RNA in vitro: a new type of naturally occurring substrate for the ribozyme.

We have found that the catalytic RNA of RNase P of Escherichia coli (M1 RNA) can cleave 2S ribosomal RNA (2S rRNA) of Drosophila melanogaster at specific positions in vitro. The cleavage mainly occurred at two sites between nucleotides 11 and 12, and between 16 and 17 of 2S rRNA. Kinetic analyses of the reaction revealed that a dimer caused by intermolecular interaction of 2S rRNA may be the substrate for the cleavage between 11 and 12, while a simple monomer is the substrate for the cleavage between 16 and 17. Substrate recognition by M1 RNA is also discussed.

Animals↗

PubMed2000

DNA-bending finger: artificial design of 6-zinc finger peptides with polyglycine linker and induction of DNA bending.

DNA structural changes such as bending play an important role in various biological reactions. Not only protein binding to its specific DNA sequence but also DNA bending induced by the protein is indispensable for unique gene expression. Therefore, an artificial protein that induces a DNA conformational change is interesting as a transcriptional regulator of a specific gene. We created 6-zinc finger proteins, Sp1ZF6(Gly)n (n = 4, 7, 10), by connecting two DNA binding domains of transcription factor Sp1 with flexible polyglycine peptide linkers, and their effects on DNA structure were compared with that of native 3-zinc finger Sp1(530-623). Gel electrophoretic methods revealed that Sp1ZF6(Gly)7 and Sp1ZF6(Gly)10 bind to two distal GC boxes and result in DNA bending. Evidently, the hydroxyl radical footprinting analysis demonstrated that hypersensitive cleavage was observed at the 5'-TA step in the intervening region bound by Sp1ZF6(Gly)7 or Sp1ZF6(Gly)10. The phasing assays strongly suggested that the induced DNA bending was directed toward the major groove and that Sp1ZF6(Gly)7 caused the most drastic directional change in DNA bending. Of special interest are the facts that the newly designed 6-finger peptides Sp1ZF6(Gly)7 and Sp1ZF6(Gly)10 can induce DNA bending at the intervening region of the two distal binding sites and that the linker length between two 3-zinc finger motifs has a crucial effect on the entire DNA-bending direction. Such DNA-bending fingers may be feasible for use as a gene expression regulator based on the structural change in DNA in the future.

Amino Acid Sequence↗

PubMed2000

Pancreatitis-associated ascitic fluid increases intracellular Ca(2+) concentration on hepatocytes.

BACKGROUND: We have reported that pancreatitis-associated ascitic fluid (PAAF) contains a cytotoxic factor(s) inducing apoptosis on renal tubular cells and hepatocytes. It has been suggested that elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)) is associated with the development of cell damage and apoptosis. METHODS: To clarify the mechanism of hepatocellular injury in acute pancreatitis, the effect of PAAF on hepatocyte [Ca(2+)](i) was investigated. Primary cultures of rat hepatocytes were loaded with Fura-2/acetoxymethyl, and the changes of [Ca(2+)](i) were measured using spectrofluorometer. RESULTS: The baseline of hepatocyte [Ca(2+)](i) was 172 +/- 17 nM. [Ca(2+)](i) increased from 1 min after the addition of PAAF in a dose-dependent manner. Fractionation of PAAF revealed only one fraction (molecular weight >/= 5 x 10(4)) possessed both [Ca(2+)](i) elevation activity and cytotoxic activity. Neither 8-(N,N-diethyl-amino) octyl-3,4,5-trimethoxybenzoate (TMB-8) nor thapsigargin inhibited the PAAF-evoked [Ca(2+)](i) elevation. Chelation of extracellular Ca(2+) by ethylene glycol bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) prevented the elevation of [Ca(2+)](i), but verapamil did not prevent it. Platelet-activating factor antagonist (TCV-309) blocked the PAAF-elicited [Ca(2+)](i) elevation. Pancreatitis-associated serum also increased hepatocyte [Ca(2+)](i). Moreover, PAAF increased [Ca(2+)](i) on Madin-Darby canine kidney cells in a dose-dependent manner. CONCLUSIONS: These results suggest that the dramatic elevation of hepatocyte [Ca(2+)](i) due to PAAF may be closely related to the hepatocellular injury in severe acute pancreatitis and that platelet-activating factor may play a pivotal role in increasing hepatocyte [Ca(2+)](i). Elevation of [Ca(2+)](i) in various cells may be involved in the mechanism of multiple organ failure in this disease.

Acute Disease↗

PubMed2000

The local spread of lower bile duct cancer: evaluation by thin-section helical CT.

This study illustrates the local spread of lower bile duct cancer with thin-section helical CT in correlation with the surgical and pathological findings. Pathologically, 16 patients had pancreatic invasion, 4 had small bowel mesentery invasion, 7 had extrapancreatic nerve plexus invasion, and 3 patients had vascular invasion. On thin-section helical CT, pancreatic invasion was correlated to the clarity or non-clarity of the bile duct mass-pancreas border and the presence of an intrapancreatic mass. Cases with small bowel mesentery and extrapancreatic nerve plexus invasion showed mass or stranding around the superior mesenteric artery and/or inferior pancreatoduodenal artery. Vascular invasion was seen as tumor contiguity to these vessels.

Adenocarcinoma↗

PubMed2000

Chairpersons' opinions regarding quality control of surgical faculty performance in Japanese academic surgery departments.

BACKGROUND: The governance and power structure of the department of surgery depends to a large extent on the chairperson's decisions in Japanese medical schools. This paper reports the current collective opinions of surgery department chairpersons regarding the quality assessment of surgical faculty performance. METHODS: Surveyed were 78 chairpersons of general surgery departments from 72 Japanese medical schools. Chairpersons were questioned about administrative and organizational decision making: rank order requirements for full-time surgical faculties, coordination of staff for surgical operations, and performance outcome measures. RESULTS: In all, 68 (87%) chairpersons responded. When selecting surgical faculties, publishing competence (45%) and collaborative personality (44%) were the two foremost concerns of chairpersons. Teaching experience (0%) and board certification (2%) showed the lowest rate for the first priority among the 6 elements listed. The operator was mainly decided by the chairperson (63%) whereas the rest of the operative team members were decided by either the chairperson (28%), a specialty team (38%), or attending surgeons (32%). Thirty-three chairpersons (49%) of 68 respondents used the morbidity and mortality conference as the only available approach for assessing surgical performance on a regular basis, whereas the remaining half did not have routine outcome measures. CONCLUSIONS: The results of this study indicate that surgery department chairpersons deemed collaborative personality and publishing competence the two major requirements for candidates of surgical faculties. Although the morbidity and mortality conference is currently the only available approach for assessing surgical performance, the majority of chairpersons felt that outcome measures should be based on more objective and structured criteria.

Academic Medical Centers↗

PubMed2000

Selective vulnerability to radiation in the hippocampal dentate granule cells.

BACKGROUND: Radiation therapy is an effective approach in the treatment of highly radiosensitive brain tumors such as germinomas. However, recent studies have reported intellectual disturbances in patients who underwent whole-brain irradiation as children. We detected apoptosis in the infantile murine cerebrum after systemic X-ray irradiation. METHODS: Subjects were 100 ICR mice 4 weeks old, of which 90 were systemically exposed to 18 Gy X-rays (0.45 Gy/min); 10 each were decapitated and the cerebrums were removed 1, 3, 6, 9, 12, 18, 24, 48, and 72 hours after irradiation. Controls were 10 unirradiated mice. DNA fragmentation analysis was carried out by agarose gel electrophoresis, and morphological analysis was by the TUNEL method. RESULTS: According to agarose gel electrophoresis, the cerebral DNA ladders were detected only over 6 to 24 hr, peaking in 9 hr. Even at the peak, band intensity was nearly double that of the unirradiated normal thymus. According to the TUNEL analysis, radiation-induced apoptosis increased, with a peak at 9 hours, but decreased 24 hours after irradiation. Apoptotic cells were always localized exclusively in the hippocampal dentate granule cells. CONCLUSIONS: We found that vulnerability to radiation existed in the hippocampal dentate granule cells. Intellectual disturbances in patients who have undergone whole-brain irradiation may be caused by injury to the hippocampus.

Acute Disease↗

PubMed2000

Human malignant melanoma cells release a factor that inhibits the expression of smooth muscle alpha-actin.

Smooth muscle alpha-actin (SMA) is a cytoskeletal protein expressed in vascular smooth muscle cells, pericytes, hair follicle dermal sheaths and myofibroblasts which appear in the process of wound healing and tumor growth. To examine the effect of malignant melanoma on the expression of SMA in these non-neoplastic cells, we carried out immunohistochemical staining and a cell culture study. Conditioned medium prepared from a melanoma cell line M14 was incubated with a rat fibroblastic cell line 3Y1, which had been shown to express SMA. Human cells that had migrated from nevus tissue were also cultured either with or without M14 conditioned medium. Immuno-histochemical staining of human melanoma tissues suggested that the expression of SMA was low in the vicinity of the tumor as well as within the tumor nodules. The conditioned medium from melanoma, but not the medium from control non-neoplastic cells, suppressed the expression of SMA both in the 3Y1 cells and human cells that migrated from the nevus. Preincubation of the medium with anti-platelet-derived growth factor allowed 76% recovery of SMA expression. These data thus imply that melanoma cells release a platelet-derived growth factor-like substance which has a suppressive effect on the contractile elements in non-neoplastic cells.

Actins↗

PubMed2000

Effects of capsaicin on biliary free fatty acids in rats.

The effects of capsaicin, a major pungent agent of capsicum fruits, on biliary free fatty acids (FFAs) were studied in male rats. Animals were dosed 100 mg/kg capsaicin after the administration of olive oil, and the bile was obtained for 6 hours continuously after dosing with capsaicin for analysis of FFAs using HPLC methods. Capsaicin significantly decreased the total biliary FFA concentration in the animals which had been previously increased by the administration of olive oil. The main FFAs in the bile of control rats are lauric and palmitic acids, followed by linoleic, oleic, stearic and palmitoleic acids. Capsaicin alone decreased the values of these main FFAs. While lauric, palmitic, linoleic, stearic and arachidonic acids were increased significantly by the treatment with olive oil, elevation of these FFAs was inhibited by the treatment with capsaicin.

Animals↗

PubMed2000

Serum parathyroid hormone in healthy Japanese women in relation to serum 25-hydroxyvitamin D.

The aim of this work was to clarify levels of serum parathyroid hormone (PTH) in healthy adult women and to study the relationship between PTH and 25-hydroxyvitamin D [25(OH)D]. One hundred sixty-nine healthy women aged 40 years or older in a community were studied. The average age of the subjects was 65.3 years (SD 8.2). All subjects had normal serum creatinine levels. Serum intact PTH and 25(OH)D were measured in these subjects. The mean intact PTH concentration was 2.19 pmol/l (SD 1.02). High intact PTH levels above the reference range were observed in four women (2.4%), all of whom were aged 70 years or older. Intact PTH increased with age with a correlation coefficient of 0.192 (p = 0.013). However, there was no correlation (r = -0.125, p = 0.105) between intact PTH and 25(OH)D whose concentrations were more than 37.5 nmol/l. In conclusion, PTH levels of healthy adult Japanese women are lower than previous reports from Western countries, which may be due to the high 25(OH)D levels of the present subjects and/or an ethnic difference. In addition, there is no association between serum 25(OH)D and PTH levels in this Japanese population, supporting a cutoff level of 25(OH)D less than 37.5 nmol/l for the elevated PTH level.

25-Hydroxyvitamin D 2↗

PubMed2000

Elevated plasma levels of alpha-melanocyte stimulating hormone (alpha-MSH) are correlated with insulin resistance in obese men.

OBJECTIVE: The role of alpha-melanocyte stimulating hormone (MSH) in obesity has been well-documented. However, circulating alpha-MSH concentrations in obese men and their relationship with clinical indicators of obesity and glucose metabolism have not as yet been evaluated. METHODS: We measured the plasma concentrations of alpha-MSH in 15 obese and 15 non-obese male subjects. The relationship of the plasma concentrations of alpha-MSH with body mass index (BMI), body fat mass (measured by bioelectric impedance), body fat distribution (measured by computed tomography), insulin levels, insulin resistance (assessed by the glucose infusion rate (GIR) during an euglycemic hyperinsulinemic clamp study) and with the serum concentrations of leptin and TNF-alpha were also evaluated. RESULTS: In obese men, the plasma alpha-MSH concentrations were significantly increased compared with those in non-obese men (P< 0.02). The plasma levels of alpha-MSH were positively correlated with BMI (r= 0.560, P< 0.05), fasting insulin levels (r=0.528, P< 0.05) and with visceral fat area (r=0.716, P<0.01), but negatively correlated with GIR (r= -0.625, P< 0.02) in obese male subjects. There were significant correlations between plasma concentrations of alpha-MSH and visceral fat area (r=0.631, P< 0.02), and GIR (r = -0.549, P< 0.05) in non-obese male subjects. Circulating concentrations of alpha-MSH were not significantly correlated with the serum concentrations of leptin and TNF-alpha in both obese and non-obese men. CONCLUSION: Circulating concentrations of alpha-MSH are significantly increased and correlated with insulin resistance in obese men.

Adult↗

PubMed2000

In vitro hyperprocessing of Drosophila tRNAs by the catalytic RNA of RNase P the cloverleaf structure of tRNA is not always stable?

We have previously reported that the catalytic RNA subunit of RNase P of Escherichia coli (M1 RNA) cleaves Drosophila initiator methionine tRNA (tRNA(Met)i) within the mature tRNA sequence to produce specific fragments. This cleavage was dependent on the occurrence of an altered conformation of the tRNA substrate. We call this further cleavage hyperprocessing. In the present paper, to search for another tRNA that can be hyperprocessed in vitro, we used total mature tRNAs from Drosophila as substrates for the in vitro M1 RNA reaction. We found that some tRNAs can be hyperprocessed by M1 RNA and that two such tRNAs are an alanine tRNA and a histidine tRNA. Using mutant substrates of these tRNAs, we also show that the hyperprocessing by M1 RNA is dependent on the occurrence of altered conformations of these tRNAs. The altered conformations were very similar to that of tRNA(Met)i. We show here that M1 RNA can be used as a powerful tool to detect the alternative conformation of tRNAs. The relationship between these hyperprocessing reactions and stability of the tRNA structure will also be discussed.

Alanine↗

PubMed2000

Troglitazone reduces plasma levels of tumour necrosis factor-alpha in obese patients with type 2 diabetes.

We evaluated the effect of troglitazone (given orally 400 mg/day) on glucose intolerance and on the plasma levels of tumour necrosis factor-alpha (TNF-alpha) in 12 obese patients with type 2 diabetes for 12 weeks. Troglitazone significantly decreased fasting plasma glucose, serum C-peptide, serum insulin and HbA1c levels. Plasma levels of TNF-alpha were significantly reduced by troglitazone administered for 8 and 12 weeks. Troglitazone administration significantly improved insulin resistance, but did not affect pancreatic beta-cell function as evaluated by the homeostasis model assessment (HOMA). In the present study, we reported for the first time that troglitazone administration significantly reduces plasma levels of TNF-alpha in obese patients with type 2 diabetes.

Blood Glucose↗

PubMed2000

Macrophage-derived transforming growth factor-beta1 induces hepatocellular injury via apoptosis in rat severe acute pancreatitis.

BACKGROUND: The mechanism of acute pancreatitis-induced hepatocellular injury is unclear. We have observed hepatocyte apoptosis in rat acute necrotizing pancreatitis. These studies were designed to determine the mediator(s) responsible for hepatocyte apoptosis and to clarify the significance of macrophages as its source. METHODS: A rat sodium deoxycholate-induced pancreatitis model was used. Immunohistochemical studies for apoptosis-inducing mediators on hepatocytes were examined in the liver and on the peritoneal macrophages. The levels of transforming growth factor-beta1 (TGF-beta1) were also evaluated quantitatively with an enzyme-linked immunosorbent assay. Induction of apoptosis on the hepatocytes was evaluated by in situ nick-end labeling and tissue DNA fragmentation enzyme-linked immunosorbent assay. Finally, the effects of TGF-beta1 neutralization and macrophage depletion were examined. RESULTS: In the liver and the peritoneal macrophages, strong expression of TGF-beta1 was detected early in the course of pancreatitis. In sodium deoxycholate-induced pancreatitis, the levels of TGF-beta1 were also elevated in the plasma (9.2 +/- 0.8 ng/mL), in the pancreatitis-associated ascitic fluid (11.5 +/- 0.6 ng/mL), and in the liver homogenate (2.8 +/- 0.3 ng/g of liver tissue). Moreover, the amount of fragmented DNA of the liver with pancreatitis was 290% +/- 20% of that with a sham operation and serum alanine aminotransferase levels elevated to 248.2 +/- 67.0 IU/L. TGF-beta1 neutralization partly blocked the positive labeling on the nuclei of the hepatocytes, the elevation of the amounts of fragmented DNA (205% +/- 10% of sham operation), and the serum alanine aminotransferase level (144.2 +/- 14.9 IU/L). On the other hand, the macrophage depletion caused a marked decrease in the TGF-beta1 protein level in the plasma (4.8 +/- 1.2 ng/mL) or in the pancreatitis-associated ascitic fluid (8.0 +/- 1.0 ng/mL). Moreover, the macrophage depletion completely inhibited the elevation of the TGF-beta1 protein level in the liver homogenate (1.5 +/- 0.4 ng/g of liver tissue), and thereafter decreased the amounts of the positive labeling on the nuclei of the hepatocytes and decreased the amount of fragmented DNA (120% +/- 18% of sham operation) and the serum alanine aminotransferase elevation (119.2 +/- 24.2 IU/L). CONCLUSIONS: In a model of sodium deoxycholate-induced pancreatitis, macrophages are responsible for pancreatitis-induced hepatocellular injury by means of apoptosis, and macrophage-derived TGF-beta1 is one of the major factors inducing the hepatocyte apoptosis.

Acute Disease↗

PubMed2000

Apoptotic cell death of hepatocytes in rat experimental severe acute pancreatitis.

BACKGROUND: Apoptosis of hepatocytes has been reported to be involved in liver failure complicated with systemic manifestations such as endotoxemia. We hypothesized that hepatocyte apoptosis occurs in severe acute pancreatitis. METHODS: Induction of apoptosis was evaluated in the liver from rats with necrotizing pancreatitis. Apoptosis-inducing activity of the pancreatitis-associated ascitic fluid on hepatocytes was evaluated in vivo by intraperitoneal injection of the ascitic fluid and in vitro using rat primary hepatocyte culture. RESULTS: Apoptosis was detected in hepatocytes in the rats both with severe acute pancreatitis and with the intraperitoneal injection of the ascitic fluid by in situ nick-end labeling and DNA fragmentation. Apoptotic change and hepatic injury were ameliorated by administration of an interleukin-1 beta-converting enzyme inhibitor. The ascitic fluid exhibited cytocidal activity in rat primary hepatocyte culture via apoptosis, which was confirmed by DNA fragmentation, by cell cycle analysis, and by nuclear fragmentation. The neutralizing antibody for transforming growth factor-beta 1 partially blocked the apoptosis induction but the antibody to tumor necrosis factor-alpha had no effect. CONCLUSIONS: Apoptotic cell death occurs in hepatocytes in severe acute pancreatitis partially via transforming growth factor-beta 1 in the pancreatitis-associated ascitic fluid.

Acute Disease↗