bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of interferon therapy on Japanese chronic hepatitis C virus patients with anti‐liver/kidney microsome autoantibody type 1
Authors: Iijima Yoshihiko , Kato Takanobu , Miyakawa Hiroshi , Ogino Masataka , Mizuno Makoto , Sugihara Kanji , Ando Takahiro , Fujiwara Kei , Orito Etsuro , Ueda Ryuzo , Mizokami Masashi 
Published: March 2003

AbstractAim: The aim of this study was to determine the prevalence of anti‐liver/kidney microsome autoantibody type 1 (anti‐LKM‐1) among hepatitis C virus (HCV)‐infected Japanese patients at various stages (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma), and to assess the influence of anti‐LKM‐1 on interferon therapy.Methods: A total of 390 serum samples from 215 HCV‐infected patients with chronic hepatitis (HCV‐CH), 81 HCV‐infected patients with liver cirrhosis (HCV‐LC), and 94 HCV‐HCC infected patients were subjected to examination. Ninety‐one HBsAg‐positive patients and 137 healthy subjects served as controls. Anti‐liver/kidney microsome autoantibody type 1 was determined by using a newly developed ELISA using recombinant cytochrome P450 IID6 as the antigen.Results: Anti‐liver/kidney microsome autoantibody type 1 was detected in six of the 390 (1.5%) chronic HCV‐infected patients (four were HCV‐CH and two were HCV‐LC); in contrast, it was not detected in control groups. Among the 110 HCV‐CH patients treated with interferon (IFN), four were positive for anti‐LKM‐1. No change in anti‐LKM‐1 immunoreactivity from negative to positive during interferon therapy was observed. Moreover, no increase in the serum alanine aminotransferase level was observed in these four patients with anti‐LKM‐1.Conclusion: Our study indicates that: (i) anti‐LKM‐1 does not aggravate the liver disease associated with HCV infection; and (ii) no change in anti‐LKM‐1 immunoreactivity from negative to positive or no aggravations of liver dysfunction were observed among HCV‐CH patients during the IFN therapy for Japanese patients with liver disease.
Clinicopathological features of gastric mucosa‐associated lymphoid tissue lymphoma: A comparison with diffuse large B‐cell lymphoma without a mucosa‐associated lymphoid tissue lymphoma component
Authors: Hiyama Toru , Haruma Ken , Kitadai Yasuhiko , Masuda Hiroshi , Miyamoto Masaki , Ito Masanori , Kamada Tomoari , Tanaka Shinji , Uemura Naomi , Yoshihara Masaharu , Sumii Koji , Shimamoto Fumio , Chayama Kazuaki 
Published: March 2003

AbstractBackground and Aims: The aim of this study was to clinicopathologically distinguish the pathogenesis of gastric mucosa‐associated lymphoid tissue (MALT) lymphoma and diffuse large B‐cell lymphoma without a MALT lymphoma component (DLL).Methods: We investigated clinicopathological features of these gastric lymphomas including age, sex ratio, tumor location and depth, macroscopic appearance, and infection with Helicobacter pylori of these gastric lymphomas and hepatitis viruses in 24 patients with gastric low‐grade MALT lymphoma, 10 patients with high‐grade MALT lymphoma, and 19 patients with DLL. The frequency of H. pylori infection in lymphoma patients was compared with that in age‐ and sex‐matched control subjects.Results: There was a predominance of females with MALT lymphoma (male to female ratio, 8/16 for low‐grade MALT lymphomas and 1/9 for high‐grade MALT lymphomas), and there was a predominance of males with DLL (male to female ratio, 13/6); the ratios differed significantly (P < 0.05). Ninety‐two percent of low‐grade MALT lymphomas and 80% of high‐grade MALT lymphomas were confined to the mucosal and submucosal layers, but lymphoma cells invaded the muscular layer or more deeply in 74% of DLL. Helicobacter pylori infection occurred significantly more often in patients with low‐grade MALT lymphoma than in age‐ and sex‐matched controls (96 vs 67%, P < 0.01). Conversely, the frequency of H. pylori infection in DLL patients did not differ from that in controls.Conclusions: These data suggest that H. pylori infection may be associated with the development of gastric MALT lymphoma, but not DLL, and that MALT lymphoma and DLL may have a different pathogenesis.
Perioperative changes in carbonylhemoglobin and methemoglobin during abdominal surgery: Alteration in endogenous generation of carbon monoxide
Authors: TAKEDA RYOJI , TANAKA AKIRA , MAEDA TOSHIKI , YAMAOKA YOSHIO , NAKAMURA KUMI , SANO KAORU , KATAOKA MASATO , NAKAMURA YOSHIAKI , MORIMOTO TAISUKE , MUKAIHARA SUMIO 
Published: March 2003

Abstract
Background:
Carbon monoxide (CO), which is homologous to nitric oxide (NO) as a monoxide, has been recently studied as a novel gaseous mediator for the maintenance of circulatory homeostasis and as a regulator of organ functions. Abdominal surgery is supposed to modulate the gaseous mediator by the reduction of heme oxygenase (HO) activity or transcriptional regulation of inducible HO. Therefore, we investigated perioperative changes in CO generation during abdominal surgery.
Methods:
A total of 397 patients who received abdominal surgery under intubation anesthesia were studied retrospectively by spectrophotometric analysis of carbonylhemoglobin (COHb) and methemoglobin (metHb) in arterial blood obtained at three points: before operation; several hours after return from operation room (0 POD); and next morning (1 POD). Thirty‐three splenectomies, 36 hepatectomies and 42 drainages with control of infection focus for peritonitis were compared with 286 controls. The influences of smoking and blood transfusion were disregarded in the analysis, because smoking and blood transfusion were shown to increase exogenous and endogenous CO, respectively.
Results:
In the non‐smoker control group without blood transfusion, COHb did not change during the perioperative period, while metHb increased from the preoperative value of 0.52 ± 0.03 to 0.72 ± 0.02 at 0 POD and returned to 0.45 ± 0.03 mg/dL at 1 POD. In the splenectomy group, COHb decreased from the preoperative value of 1.63 ± 0.36 to 1.19 ± 0.20 and 1.13 ± 0.26 mg/dL at 0 and 1 POD, respectively, as a result of the removal of the organ with high HO activity. In the splenectomy group MetHb remained low: 0.47 ± 0.09 mg/dL at 0 POD as compared with the control value. In the peritonitis and hepatectomy groups, COHb did not change during the perioperative period, while metHb increased to 0.64 ± 0.06 and 0.73 ± 0.10 mg/dL at 1 POD, respectively, as compared with the control value. In the hepatectomy group with or without blood transfusion, however, COHb and metHb were higher at 1 POD than the corresponding control value.
Conclusion:
Changes in COHb and metHb concentrations in arterial blood occur during abdominal surgery, although these amplitudes are small when compared with CO intoxication and methemoglobulinemia. It is likely that organ perfusion and functions are affected by these monoxide gas mediators during abdominal surgery.© 2002 Blackwell Publishing Asia Pty Ltd
Decreased production of insulin‐like growth factor‐binding protein (IGFBP)‐6 by transfection of colon cancer cells with an antisense IGFBP‐6 cDNA construct leads to stimulation of cell proliferation
Authors: KIM EUN J , SCHAFFER BEVERLY S , KANG YOUNG‐HEE , MACDONALD RICHARD G , PARK JUNG HY 
Published: March 2003

Abstract

Background
: Previously, we have observed that highly unsaturated dietary (n‐3) fatty acids inhibit cell proliferation in conjunction with stimulation of insulin‐like growth factor‐binding protein (IGFBP)‐6 secretion in Caco‐2 cells, a human colon carcinoma cell line.
Methods
: To test the converse hypothesis that inhibition of endogenous IGFBP‐6 secretion stimulates Caco‐2 cell proliferation, cells were transfected with the antisense IGFBP‐6 expression construct or pcDNA3 vector only, and single colonies resistant to G418 sulfate were isolated.
Results
: Our initial studies indicated that three antisense clones grew faster and produced less IGFBP‐6 than two pcDNA3 clones, so antisense IGFBP‐6 #5 and pcDNA3 #8 were selected for further detailed analysis. Both the control and antisense clones grew in serum‐free medium reaching a plateau density at day eight. However, the antisense clone grew at a rate faster than that of the control and reached a final density that was 31 ± 3% higher than the control. Northern blot, ligand blot and immunoblot analyses revealed that accumulation of IGFBP‐6 mRNA and concentrations of IGFBP‐6 peptide produced by the antisense clone were decreased by 80–90% compared to the control. The doubling times of the antisense and control clones were 21.9 ± 0.4 and 24.8 ± 0.3 h (P < 0.05), respectively. Exogenous IGF‐I and IGF‐II (0.2–200 nmol/L) stimulated proliferation of both the control and antisense clones in a dose‐dependent manner, but the relative potency and efficacy of IGF‐II was higher in the antisense clone compared to the control. These results indicate that suppression of IGFBP‐6 secretion correlates with an increase in the basal rate of Caco‐2 cell growth.
Conclusions
: Our findings are consistent with the hypothesis that IGFBP‐6 inhibits cell growth by binding to endogenously produced IGF‐II, thereby preventing IGF‐II from interacting with the IGF‐I receptor to stimulate cellular proliferation by an autocrine mechanism.© 2002 Blackwell Publishing Asia Pty Ltd
Reciprocal relationship between methylation status and loss of heterozygosity at the p14ARF locus in Australian and South African hepatocellular carcinomas
Authors: HERATH NIRMITHA I , KEW MICHAEL C , WALSH MICHAEL D , YOUNG JOANNE , POWELL LAWRIE W , LEGGETT BARBARA A , MACDONALD GRAEME A 
Published: March 2003

Abstract Chromosome 9p21, a locus comprising the tumor suppressor genes (TSG) p16INK4a
and p14ARF, is a common region of loss of heterozygosity (LOH)
in hepatocellular carcinoma (HCC). p14ARF shares exon 2 with p16
in a different reading frame. p14 binds to MDM2 resulting in a stabilization of functional
p53. This study examined the roles of p14, p16 and p53 in hepatocarcinogenesis,
in 37 Australian and 24 South African patients. LOH at 9p21 and 17p13.1, p14
and p16 mutation analysis, p14 and p16 promoter methylation
and p14, p16 and p53 protein expression was examined. LOH at 9p21 was detected more
frequently in South African HCC (P = 0.04). Comparable rates of p53
LOH were observed in Australian and South African HCC (10/22, 45%vs
13/22, 59%, respectively). Hypermethylation of the p14 promoter was
more prevalent in Australian HCC than in South African HCC (17/37, 46%vs
7/24, 29%, respectively). In Australian HCC the prevalence of p14
methylation increased with age (P = 0.03). p16 promoter methylation
was observed in 12/37 (32%) and 6/24 (25%) in Australian and South
African HCC, respectively. Loss of p16 protein expression was detected in 14/36 Australian
HCC whereas p53 protein expression was detected in 9/36. Significantly, a reciprocal
relationship between 9p21 LOH and p14 promoter hypermethylation was observed
(P≤0.05). No significant association between p14 and p53 was seen in this study. The reciprocal relationship identified indicates different pathways of tumorigenesis and likely reflects different etiologies of HCC in the two countries.© 2002 Blackwell Science Asia Pty Ltd
Update on the management of Helicobacter pylori infection, including drug‐resistant organisms
Authors: Goh KL 
Published: March 2003

Abstract  Helicobacter pylori infection has many different clinical outcomes. Not all infected persons need to be treated. Therefore, indications for treatment have to be clear, and several consensus guidelines have been formulated to aid the medical practitioner in this decision‐making process. Triple therapy with a proton pump inhibitor (PPI), in combination with amoxicillin and clarithromycin is the established treatment of choice. For patients with penicillin hypersensitivity, metronidazole can be substituted for amoxicillin. Bacterial resistance to antibiotics is a major factor adversely affecting treatment success. Resistance to metronidazole has been reported in up to 80%, and resistance to clarithromycin in 2–10% of strains cultured. Resistance to either one of the antibiotics has been reported to result in a drop in efficacy of up to 50%. Emergence of resistance to both metronidazole and clarithromycin following failed therapy is a cause for concern; this underlines the need to use the best available first‐line therapy. To avoid the emergence of resistance to both key antibiotics, the combination of metronidazole and clarithromycin should be avoided where possible. For failed treatment, several strategies can be employed. These include ensuring better compliance with repeat therapy, and maximizing the efficacy of repeat treatment by increasing dosage and duration of treatment, as well as altering the choice of drugs. Quadruple therapy incorporating a bismuth compound with a PPI, tetracycline and metronidazole has been a popular choice as a ‘rescue’ therapy. Ranitidine bismuth citrate has been shown to be able to overcome metronidazole and clarithromycin resistance; it may be a useful compound drug to use in place of a PPI in ‘rescue’ therapies. In the case of persistent treatment failures, it is useful to consider repeating gastroscopy and obtaining tissue for culture, and then prescribe antibiotics according to bacterial susceptibility patterns. It is also important in refractory cases to review the original indication for treatment and determine the importance of the indication.© 2002 Blackwell Publishing Asia Pty Ltd
Randomized comparative study of omeprazole and famotidine in reflux esophagitis
Authors: Kawano Sunao , Murata Hiroaki , Tsuji Shingo , Kubo Mitsuhiko , Tatsuta Masaharu , Iishi Hiroyasu , Kanda Tsutomu , Sato Tomonobu , Yoshihara Harumasa , Masuda Eiji , Noguchi Masahiko , Kashio Shinji , Ikeda Masahiro , Kaneko Akira 
Published: March 2003

AbstractBackground: Although proton pump inhibitors (PPI) and H2‐receptor antagonists (H2‐RA) are routinely used in the treatment of reflux esophagitis (RE), no consensus has been reached yet as to whether the first‐choice drug should be PPI or H2‐RA. In this study, the effects of omeprazole (OMP) and famotidine (FAM) on RE have been examined in a randomized comparative study.Methods: Protocols of OMP 20 mg once daily or FAM 20 mg twice daily for 8 weeks were allocated to 56 cases with RE at random, using an envelope randomization method. Their efficacy in achieving healing was examined endoscopically and a relief from subjective symptoms was compared.Results: Patient's background such as sex, age, recurrence, hiatal hernia, smoking and drinking habits, and complications, and the severity of esophagitis at the time of enrolment were not significantly different between the two groups. Healing in the OMP group and the FAM group was observed in 72 and 32% (P = 0.025) of patients at week 4 and 95 and 53% (P = 0.003) of patients at week 8, respectively. Subjective symptoms were relieved more frequently in the OMP group (at week 2, 67% compared with 29%, P = 0.005; at week 4, 95% compared with 55%, P = 0.009), but this superiority was not significant at week 8 (94% compared with 65%, P = 0.085). No serious adverse events occurred.Conclusions: Omeprazole provided quicker healing and a greater relief from subjective symptoms than did FAM in the treatment of RE, and was considered more suitable as a first‐choice drug.© 2002 Blackwell Publishing Asia Pty Ltd
Efficacy of granulocyte‐macrophage colony‐stimulating factor or lamivudine combination with recombinant interferon in non‐responders to interferon in hepatitis B virus‐related chronic liver disease patients
Authors: GUPTAN RAJKUMAR C , THAKUR VARSHA , KAZIM SEYED N , SARIN SHIV K 
Published: March 2003

Abstract
Background and Aims
: Non‐response to interferon (IFN) monotherapy is a major therapeutic problem in the management of chronic hepatitis B infection. The efficacy of combination therapy to enhance the immunomodulatory effect of IFN by combining granulocyte‐macrophage colony‐stimulating factor (GMCSF) or decreasing viral load by adding an antiviral agent such as lamivudine was evaluated prospectively.
Methods
: Twenty‐four patients with chronic hepatitis B who were non‐responders to previous IFN therapy were randomized to receive an IFN and GMCSF (group A, n = 10) or IFN and lamivudine (group B, n = 14) combination for 6 months. The end‐of‐treatment response was assessed by hepatitis B virus (HBV)‐DNA and hepatitis B e antigen (HBeAg) determination.
Results
: All patients successfully completed both the treatment schedules. The mean age, alanine aminotransferase (ALT) levels, liver histology, HBV‐DNA levels and distribution of HBV genotypes were comparable between the two groups. At the end of treatment there was a significant decrease in mean ALT levels. The HBV‐DNA and HBeAg loss was seen in six of 10 (60%) patients in group A and in seven of 14 (50%) patients in group B. During a mean follow‐up of 15 ± 3 months, two of six (33%) patients in group A and three of seven (43%) patients in group B relapsed with HBV‐DNA and HBeAg positivity, which meant an overall sustained response of 40% and 28%, respectively. None of the factors such as HBV viral load, ALT levels or liver histology could predict the non‐response to combination therapy or occurrence of relapse. There was a trend in patients with genotype A compared with genotype D towards non‐response to therapy, although the difference was not significant.
Conclusions
: The combination of IFN plus GMCSF or lamivudine was effective in non‐responders to IFN monotherapy. Larger studies using such combination therapies would be helpful in improving treatment strategies for chronic hepatitis B.© 2002 Blackwell Publishing Asia Pty Ltd
High, but not low, dietary retinoids aggravate manifestation of rat liver fibrosis
Authors: VOLLMAR BRIGETTE , HECKMANN CHRISTINE , RICHTER SVEN , MENGER MICHAEL D 
Published: March 2003

Abstract
Background
: Although there is strong implication that retinoids regulate Ito cell proliferation and collagen synthesis, results from in vivo studies on the relationship between vitamin A and liver fibrosis are conflicting. The present study focuses on the role of vitamin A in carbon tetrachloride (CCl4)‐induced fibrosis by chronic feeding of rats with either a vitamin A‐supplemented or ‐depleted diet.
Methods and results
: In animals with high dietary hepatic retinoid levels, liver fibrosis was more pronounced and was associated with an increased CCl4‐toxicity resulting in high mortality (73%). Enhanced liver fibrosis was confirmed by in vivo fluorescence microscopic determination of both collagen deposits (7.4 ± 1.1 vs 3.9 ± 0.3% in high vitamin A diet‐fed and standard diet‐fed fibrotic animals, respectively; P < 0.05) and rarefication of sinusoids (1.5 ± 0.2 vs 2.4 ± 0.2 sinusoids/200 µm in high vitamin A diet‐fed and standard diet‐fed fibrotic animals, respectively; P < 0.05). It was further associated with decreased bile flow and increased parenchymal cell damage. CCl4 reduced hepatic retinoid levels in high vitamin A diet‐fed animals, but restored hepatic retinoid levels in animals fed with a vitamin A‐deficient diet, implying major interference of vitamin A metabolism with hepatotoxic agents such as CCl4. Low vitamin A feeding did not modulate liver fibrogenesis and caused no mortality.
Conclusions
: These results show that the vitamin A status of the liver plays an important role in liver fibrogenesis. While dietary vitamin A shortage does not promote liver fibrogenesis, high levels of vitamin A have the potential to increase systemic and hepatic toxicity of CCl4. Thus, the narrow therapeutic window for nutritional vitamin A substitution must take into account that liver fibrotic patients may display enhanced susceptibility to the adverse effects of vitamin A.© 2002 Blackwell Publishing Asia Pty Ltd
Hepatic nodules with early enhancement during computed tomography portography: Report of six cases
Authors: TAKAYASU KENICHI , MURAMATSU YUKIO , WAKAO FUMIHIKO , MIZUGUCHI YASUNORI , IWATA RYOKO , MAEDA TETSUO , MORIYAMA NORIYUKI , SAKAMOTO MICHIIE 
Published: March 2003

Abstract
Aim:
To study the clinicopathologic characteristics of hepatic nodular lesions with high attenuation (increased portal blood flow) compared with surrounding hepatic parenchyma on computed tomography (CT) during arterial portography (CTAP).
Methods
:  For six lesions found in six patients demonstrated as a high‐attenuated mass by CTAP, CT during hepatic arteriography (CTHA; n = 3 patients), digital subtraction hepatic arteriography (n = 6) and conventional helical CT (n = 6) were evaluated retrospectively and compared with histopathologic findings (n = 4). Pathologic diagnosis was atypical adenomatous hyperplasia, nodule‐in‐nodule hepatocellular carcinoma (HCC) in one resected lesion each and overt HCC in two biopsied lesions. Two patients did not undergo any therapy and were followed up.
Results
:  The average size of lesions was 2.2 cm (range 1.2–3.5 cm). The CTAP revealed high attenuation in all six lesions; entirely within the lesion (n = 4 lesions) or peripherally with a central low attenuation (n = 2). In contrast, CTHA showed low attenuated lesions; entirely within the mass (n = 2) or peripherally with a central high‐attenuated spot (n = 1). Hepatic arteriogram revealed only two hypervascular lesions; entirely and partially in one each. In the arterial phase of helical CT, all but one lesion were iso‐ or hypo‐attenuated. In two patients who were followed up to 39 and 55 months without therapy, neither tumor growth nor hemodynamic change of the lesion was recognized on CT.
Conclusions:

Even though the incidence of hepatic nodular lesions demonstrated as high attenuating on CTAP is low, all but one lesion in the current series showed iso‐ or hypo‐attenuation on CTHA and/or helical CT, suggesting the hemodynamics are reciprocal between CTAP and CTHA. One exceptional lesion that showed high attenuation on both CTAP and conventional CT was pathologically advanced HCC. Based on the follow‐up study of two untreated patients, this kind of lesion with high attenuation on CTAP seems to grow slowly.© 2002 Blackwell Publishing Asia Pty Ltd
Dysplasia and carcinoma development in a repeated dextran sulfate sodium‐induced colitis model
Authors: Okayasu Isao , Yamada Masahiro , Mikami Tetuo , Yoshida Tsutomu , Kanno Jun , Ohkusa Toshifumi 
Published: March 2003

AbstractBackground: As an important mechanism underlying the increased risk of colorectal carcinoma development in patients with long‐standing ulcerative colitis, promotion as a result of the regenerative process has been proposed. In the present study, a dysplasia‐carcinoma sequence in a novel repeated colitis model in mice is documented.Methods: Repeated colitis was induced by nine administration cycles of 3% dextran sulfate sodium (DSS; molecular weight, 54 000): each administration cycle comprised 3% DSS for 7 days followed by distilled water for the subsequent 14 days, to give conditions similar to the clinically observed active and remission phases in humans.Results: Multiple colorectal tumors (nine low‐ and four high‐grade dysplasias and two carcinomas) developed in 25 mice. These neoplastic lesions consisted of tubular structures, presenting as various types of elevated, flat and depressed tumor, similar to those in ulcerative colitis patients. A time‐course study with assessment of the severity of colitis and in vivo bromodeoxyuridine uptake during a single 3% DSS administration cycle revealed a high level of regenerative activity in the colitis‐affected mucosal epithelia.Conclusion: Thus, with the present repeated colitis model, regeneration and neoplastic lesions were apparent, the biological features of which provide evidence of a colorectal dysplasia–invasive carcinoma sequence in ulcerative colitis.