Clinical features of hepatocellular carcinoma that occur after sustained virological response to interferon for chronic hepatitis C

Background and Aim: This study investigated the clinical features of hepatocellular carcinoma in patients with sustained virological response to interferon for hepatitis C viral (HCV) infection. Methods: A total of 7715 patients with HCV infection were treated with interferon and followed up for more than 1 year after withdrawal of interferon in 64 Japanese hospitals and clinics between July 1988 and August 2001. Sustained virological response was obtained in 2515 (32.6%) patients. Of these 2515 patients, clinical data were collected for 38 patients in whom hepatocellular carcinoma developed. Sustained virological response was defined as HCV RNA negativity more than 6 months after the termination of interferon. Results: All patients were HCV RNA negative at the time of diagnosis of hepatocellular carcinoma. The median period until the detection of hepatocellular carcinoma was 4.7 years (range 1.4–9.0 years). There were significant improvements in hepatic function including serum albumin, aspartate aminotransferase, alanine aminotransferase, indocyanine green test, platelet count and histological activity grade in comparison with those before interferon therapy and at the onset of hepatocellular carcinoma. The maximum tumor size in patients without medical follow‐up for 1 year or more (median: 60 mm) was significantly larger than in patients who were periodically followed up for 6 months or less (median: 25 mm) (P = 0.002). Conclusions: The present findings emphasize the importance of regular medical follow up of patients with HCV infection, as even patients showing a sustained virological response to interferon and in whom hepatic function has improved have the potential to develop hepatocellular carcinoma.     

Effects of famotidine and cimetidine on plasma levels of epidurally administered lignocaine

The effects of two H2-receptor antagonists, famotidine and cimetidine, on the plasma levels of epidurally administered lignocaine were studied. Group A (n = 20) received famotidine 20 mg orally the night before surgery and 20 mg intramuscularly 60 minutes before induction of anaesthesia. Group B (n = 15) received cimetidine 200 mg orally the night before the surgery and 400 mg orally 60 minutes before the anaesthetic induction. Group C (n = 20) received neither famotidine nor cimetidine and served as controls. Twelve millilitres of 2.0% lignocaine with adrenaline 1:200,000 was injected into the epidural space in all patients, after the establishment of general anaesthesia with nitrous oxide, oxygen, and enflurane (0.3-0.5%). The patients who received cimetidine showed significantly higher plasma concentrations of lignocaine compared with either group A or group C at all investigation times (p less than 0.01). The mean peak plasma concentrations were 2.4 (SEM 0.1), 3.2 (SEM 0.2) and 2.3 (SEM 0.1) micrograms/ml in group A, B, and C, respectively. This study suggests that famotidine is preferable to cimetidine for control of gastric acidity before the use of lignocaine as the epidural anaesthetic.     

Functional analysis of titin/connectin N2-B mutations found in cardiomyopathy

Hypertrophic cardiomyopathy and dilated cardiomyopathy are two major clinical phenotypes of “idiopathic” cardiomyopathy. Recent molecular genetic analyses have now revealed that “idiopathic” cardiomyopathy is caused by mutations in genes for sarcomere components. We have recently reported several mutations in titin/connectin gene found in patients with hypertrophic cardiomyopathy or dilated cardiomyopathy. A hypertrophic cardiomyopathy-associated titin/connectin mutation (Arg740Leu) was found to increase the binding to actinin, while other dilated cardiomyopathy-associated titin/connectin mutations (Ala743Val and Val54Met) decreased the binding to actinin and Tcap/telethonin, respectively. We also reported several other mutations in the N2-B region of titin/connectin found in hypertrophic cardiomyopathy and dilated cardiomyopathy. Since the N2-B region expresses only in the heart, it was speculated that functional alterations due to the mutations cause cardiomyopathies. In this study, we investigated the functional changes caused by the N2-B region mutations by using yeast-two-hybrid assays. It was revealed that a hypertrophic cardiomyopathy-associated mutation (Ser3799Tyr) increased the binding to FHL2 protein, whereas a dilated cardiomyopathy-associated mutation (Gln4053ter) decreased the binding. In addition, another TTN mutation (Arg25618Gln) at the is2 region was found in familial DCM. Because FHL2 protein is known to tether metabolic enzymes to N2-B and is2 regions of titin/connectin, these observations suggest that altered recruitment of metabolic enzymes to the sarcomere may play a role in the pathogenesis of cardiomyopathies.     

Immunogenicity and reactogenicity of the component acellular pertussis vaccine produced by a combination of column purified pertussis toxin and filamentous haemagglutinin

This is the report on a prospective, single blind, comparative study of a component acellular pertussis vaccine produced by a combination of detoxified, column purified pertussis toxin (PT) and filamentous hemagglutinin (FHA) combined with diphtheria and tetanus toxoids (DTcaP) and the traditional acellular pertussis vaccine produced with essentially the same method as described by Sato with DT (DTaP) of the same manufacturer. A total of 616 infants and children received DTcaP and a total of 289 received DTaP. In all age groups for both vaccines values of serum antibodies to PT and FHA after two doses of the vaccines were comparable to those of convalescent sera. Incidences of systemic and local reactions were, in general, not greatly different between DTcaP and DTaP recipients. In Japan the use of traditional acellular vaccines replaced whole cell vaccines in 1981. Protective antigens of Bordetella pertussis have now been specified and thus component vaccines have become theoretically possible. This is the first component vaccine which has been developed in Japan. Several other component vaccines are now under investigation in the world.     

海洋真菌96F197抗癌活性成分研究

目的对海洋真菌代谢产物中抗癌活性成分进行分离和结构鉴定,并对得到的化合物进行体外抗癌活性评价。方法用硅胶、SephedaxHL-20、ODS柱色谱及制备高效液相色谱等方法进行分离,通过化合物的理化性质及各种光谱技术鉴定化合物的结构。采用MTT法测定化合物体外抗癌活性。结果从真菌菌丝体的丙酮提取物中分离得到两个生物碱类化合物和两个甾醇类化合物,分别鉴定为viridicatol(1)、sclerotiamide(2)、22E-5α,6α-环氧麦角甾-8(14),22-二烯-3β,7α-二醇(3)、22E-5α,8α-桥二氧麦角甾-6,22-二烯-3β-醇(4)。化合物3和4在50μg·mL-1的质量浓度下可以明显地抑制HepG2、人乳腺癌MCF-7细胞和NCI-H460肿瘤细胞的生长。结论化合物3和4有明显的体外抗癌作用。     

Malignant Mesenchymoma of the Liver with Hypercalcemia Report of a Case

A case of malignant mesenchymoma of the liver is reported. Thediagnosis was confirmed on the surgical specimen. The patientshowed marked hypercalcemia. Parathyroid hormone assay was negative.     

Characteristics of obese children with low content of arachidonic acid in plasma lipids

BACKGROUND: Although there have been many studies on the relationship between obesity and long-chain polyunsaturated fatty acid (LCPUFA), the results and their interpretation are controversial, especially in children. Arachidonic acid (AA), the product of n-6 LCPUFA, is reported to be related to insulin resistance. The purpose of the present paper was to investigate the LCPUFA profile in obese children and mechanisms that contribute to reduced AA content. METHOD: An age- and sex-matched control study was performed. The study subjects were 59 obese children (mean age, 11.8 years) and 53 healthy non-obese children (mean age, 12.5 years). The study parameters included anthropometric measurements, serum lipids, leptin and fatty acid composition in plasma. RESULTS: Plasma fatty acids in obese children had lower linoleic acid (P < 0.0001) and higher dihomo-gamma-linolenic acid (P = 0.0004) than those in non-obese children. In all subjects combined, delta-6 desaturase (D6D) index (ratios of [C 18:3n-6+C 20:2n-6]/C 20:4n-6 or C 20:4n-6/C 18: 2n-6) correlated with leptin (P < 0.0001). There was no significant difference in AA content between obese and non-obese. However, the AA content was low (相似文献   

Detection of invasive protein profile of Streptococcus pyogenes M1 isolates from pharyngitis patients

Hasegawa T, Okamoto A, Kamimura T, Tatsuno I, Hashikawa S‐N, Yabutani M, Matsumoto M, Yamada K, Isaka M, Minami M, Ohta M. Detection of invasive protein profile of Streptococcus pyogenes M1 isolates from pharyngitis patients. APMIS 2010; 118: 167–78. Streptococcal toxic shock syndrome (STSS) is a re‐emerging infectious disease in Japan and many other developed countries. Epidemiological studies have revealed that the M1 serotype of Streptococcus pyogenes is the most dominant causative isolate of STSS. Recent characterization of M1 isolates revealed that the mutation of covS, one of the two‐component regulatory systems, plays an important role in STSS by altering protein expression. We analyzed the M1 S. pyogenes clinical isolates before or after 1990 in Japan, using two‐dimensional gel electrophoresis (2‐DE) and pulsed‐field gel electrophoresis (PFGE). PFGE profiles were different between the isolates before and after 1990. Markedly different profiles among isolates after 1990 from STSS and pharyngitis patients were detected. Sequence analysis of two‐component regulatory systems showed that covS mutations were detected not only in STSS but also in three pharyngitis isolates, in which proteins from the culture supernatant displayed the invasive type. The mutated CovS detected in the pharyngitis isolates had impaired function on the production of streptococcal pyrogenic exotoxin B (SpeB) analyzed by 2‐DE. These results suggest that several covS mutations that lead to the malfunction of the CovS protein occurred even in pharyngeal infection.     

Synthesis and central nervous system actions of thyrotropin-releasing hormone analogs containing a 1-substituted 2-oxoimadazolidine moiety*

A series of thyrotropin-releasing hormone (TRH) analogs in which the pyroglutamic acid residue was replaced by (S)-2-oxoimidazolidine-4-carboxylic acid (Oic-OH) and the related derivatives was prepared, and the central nervous system (CNS) actions were examined. Of these, 1-benzyl-Oic-His-Pro-NH₂ (2c) showed the most potent activities, which were 1.5-8 times greater than those of TRH. Moreover, the thyrotropin (TSH)-releasing activity of 2c was about 1/16 times weaker than that of TRH.