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Biomedical subjects

Shigeru Kohno

Publications and source records attributed to Shigeru Kohno.

At least 289 records · Page 16Linked to original sources

[Haemostatic molecular markers].

Because a significant number of the deaths caused by acute (massive) pulmonary thromboembolism occur within the hours after the onset of symptoms, its early diagnosis is very important. The gold standard diagnostic tests for venous thromboembolism (VTE), contrast venography and pulmonary angiography, respectively, are invasive, expensive, not readily available, and labor intensive. A diagnostic tool for VTE is needed that is noninvasive and highly accurate, allowing immediate treatment decisions to be made in most cases. D-dimer, a one of haemostatic molecular markers, is specific cross linked fibrin derivatives. This is the most promising blood test for VTE screening. Although elevated concentrations of D-dimers are sensitive for the presence of VTE, they are not specific. They therefore cannot be used to make a positive diagnosis of VTE.

Acute Disease↗

[Clinical evaluation of bronchial asthma complicated with sarcoidosis].

The clinical features of 25 asthma cases complicated with sarcoidosis were evaluated retrospectively. In our department, 8 patients (6%) out of 134 with sarcoidosis had asthma. The complication was found more frequently in females than in males, and the age of onset of the asthma extended from 2 to 63 years. Neither the severity nor the type of asthma showed any distinct pattern. In terms of chest radiographs of sarcoidosis, stage II was more common in our cases, while stage I was more common in the reported cases. In our cases, the severity of the asthma remained stable irrespective of the activity of the sarcoidosis. In the reported cases, the two diseases showed similar courses. The deterioration of each disease was associated in few cases with improvement in the other. In summary, the present study suggests that inflammation of the airways in asthma and sarcoidosis probably affect their course so that the two diseases improve or deteriorate together.

Adolescent↗

[Results of survey of adult community-acquired pneumonia utilizing flow chart of diagnostic guideline for management of respiratory infections].

We performed a nationwide survey of 1,258 patients to assess the treatment of community-acquired pneumonia in Japan. Cases were classified as bacterial pneumonia in which the causal organism was unknown (Type A) or presumed (Type B), atypical pneumonia (Type C), severe pneumonia (Type D), or pneumonia in certain specific morbid states (Type E). Our objectives were to assess the actual use of antimicrobials and to determine the usefulness of the "Guidelines on Respiratory Infections--Basic Concepts in the Medical Care of Community-Acquired Pneumonia in Adults", developed by the Guideline-Drafting Committee of the Japanese Respiratory Society (JRS), in differentiating these categories of patients. We also hoped to elicit constructive opinions that would contribute to future revisions of these guidelines. The findings showed that pneumonia was classified as "bacterial pneumonia in which the causal organism was unknown" in approximately half (50.2%) of the patients studied. The next most common classification was "severe pneumonia", followed by "atypical pneumonia", "bacterial pneumonia in which the causal organism was presumed", and "pneumonia in certain specific morbid states", in that order. Our results suggest that the JSR guidelines, including the methods for differentiating between bacterial pneumonia and atypical pneumonia, are useful and appropriate, and that antimicrobial agents were generally selected in accordance with the guidelines. We also identified a number of issues to be addressed in future updates of the guidelines, including criteria for physiological assessment, handling of cases in which physical findings and laboratory test results are not in agreement, age-related issues (especially the treatment of patients 65 years of age and older), the differentiation between bacterial pneumonia and atypical pneumonia, the weighing of underlying diseases and complications, and guidelines regarding the use of adjuvant therapy.

Adolescent↗

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2001)].

From October 2001 to September 2002, we collected the specimen from 370 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of the isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 458 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 456 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 69, Streptococcus pneumoniae 72, Haemophilus influenzae 85, Pseudomonas aeruginosa (non-mucoid) 44, P. aeruginosa (mucoid) 13, Klebsiella pneumoniae 32, Moraxella subgenus Branhamella catarrhalis 32, and others. Of 69 S. aureus strains, those with 4 micrograms/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 43.5%. Vancomycin and arbekacin showed the most potent activities against MRSA as observed in 2000. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 59.7% and both rates of PISP and PRSP were the highest after 1992. Carbapenems had strong activities against S. pneumoniae. Especially, panipenem and imipenem inhibited the growth of all 72 strains at 0.125 and 0.5 microgram/mL, respectively. Generally, all drugs had strong activities against H. influenzae with MIC90s of 16 micrograms/mL or less. The drug that had the strongest activity against H. influenzae was levofloxacin, which inhibited the growth of 80 of the 85 strains at 0.063 microgram/mL. Against P. aeruginosa mucoid strain, meropenem had a strong activity with MIC90 of 0.5 microgram/mL while, against non-mucoid strain, tobramycin had a strong activity with MIC90 of 2 micrograms/mL. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and minocycline, and the MIC90s were 4 micrograms/mL or less. Particularly, cefmenoxime, cefpirome, and imipenem had the strongest activity (MIC90: 0.125 microgram/mL), and cefozopran had a strong activity, inhibiting the growth of all strains at 0.25 microgram/mL. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC90s of all drugs were 4 micrograms/mL or less. The drug that had the strongest activity was minocycline and levofloxacin inhibiting all 32 strains at 0.063 microgram/mL. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (40.5%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 39.2% and 37.3% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (19.3%) and S. pneumoniae (19.9%). In contrast, H. influenzae (22.0%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (20.8%) and H. influenzae (21.5%). S. pneumoniae and H. influenzae decreased after the initiation of drug administration while S. aureus increased. The isolation frequency of P. aeruginosa was higher after than before the initiation of drug administration. The bacteria were frequently isolated from the patients who had already treated with cephems were S. aureus and P. aeruginosa. From the patients who had already treated with macrolides, S. pneumoniae was the most frequently isolated while S. aureus was the most frequently isolated from the patients pre-treated with quinolones.

Adult↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2001). I. Susceptibility distribution].

The bacterial strains isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between the period of September and December 2001. Then, the susceptibilities of them to a variety of antimicrobial agents were investigated. The number of them were 496 strains. The breakdown of these strains was Gram-positive bacteria as 29.6% and Gram-negative bacteria as 70.4%. Susceptibilities of these bacteria to antimicrobial agents were as follows; against Staphylococcus aureus, vancomycin (VCM) showed a strong activity, and this drug also had a strong activity against MRSA in preventing growth of all strains at 1 microgram/mL. In addition, arbekacin (ABK) showed strong activity with the MIC90 of 2 micrograms/mL against MRSA and prevented growth of all strains at 4 micrograms/mL. ABK also showed a strong activity against Staphylococcus epidermidis in preventing growth of all strains at 0.5 microgram/mL. Ampicillin (ABPC) and cefozopran (CZOP) showed a relatively strong activity against S. epidermidis (MIC90: 8 micrograms/mL). ABPC, imipenem (IPM), and VCM showed strong activities against Enterococcus faecalis. No increase of low-susceptible strains in E. faecalis was observed against these antimicrobial agents. Against Escherichia coli, carbapenems showed the highest activities: meropenem (MEPM) prevented growth of all strains at 0.25 microgram/mL; IPM prevented growth of all strains at 0.5 microgram/mL. CZOP and cefotiam (CTM) also showed strong activities against E. coli: MIC90 of CZOP was within 0.125 microgram/mL; MIC90 of CTM was within 0.5 microgram/mL. Quinolone-resistant E. coli was detected at frequency of 9.3%, which was lower than that in the last year, and was higher level than those in up to 1999. MEPM showed the strongest activity against Citrobacter freundii in preventing growth of all strains at 0.125 microgram/mL. Almost all drugs showed strong activities against Klebsiella pneumoniae and Proteus mirabilis, and MEPM prevented growth of all strains within 0.125 microgram/mL. Against Serratia marcescens, the MIC90 of gentamicin (GM) was the lowest value being 2 micrograms/mL, and those of IPM and carumonam were 8 and 16 micrograms/mL, respectively. Against Pseudomonas aeruginosa, almost all drugs were not so active. The MIC90 of GM was 8 micrograms/mL, those of IPM and amikacin were 16 micrograms/mL, and those of all other drugs were over than 32 micrograms/mL.

Anti-Bacterial Agents↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2001). II. Background of patients].

Five-hundred thirty one bacterial strains isolated from 412 patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between September and December 2001. Then, the clinical background of patients were investigated such as sex, age, and type of infections, infections and kind of bacteria, frequency of bacteria isolation by age and infections, bacteria and infections by timing of antibiotics administration, and bacteria and infections by surgical procedures. With regard to the relationship between age and sex of patients and type of infections, the number of cases aged lower than 50 years was few and complicated UTIs without indwelling catheter was the most frequent in male patients. In females, the number of patients aged lower than 20 years was few. Most of female patients aged lower than 80 years had uncomplicated UTIs. As for the relationship between type of infections and kind of bacteria, Escherichia coli decreased as the infections were more complicated, and Pseudomonas aeruginosa and Enterococcus faecalis increased as the infections were more complicated. In relation of these results to age of patients, isolation frequency of E. coli gradually decreased with aging in patients aged 20 years and older with uncomplicated UTIs. The isolation frequencies of E. faecalis decreased with aging in the patients with complicated UTIs without indwelling catheter while P. aeruginosa decreased with aging in the patients with complicated UTIs with indwelling catheter. E. coli was isolated a few after administration of antibiotics, and P. aeruginosa and E. faecalis were frequently isolated after administration in the patients with all types of infections. As for type of causative organisms in UTIs and with or without surgical operation, E. coli was frequently isolated in the patients without surgery in the patients with uncomplicated UTIs and complicated UTIs without indwelling catheter, while P. aeruginosa was frequently isolated in the patients who underwent surgery in the patients with uncomplicated UTIs and complicated UTIs with indwelling catheter. In uncomplicated UTIs, isolation frequencies of Klebsiella spp., P. aeruginosa, and E. faecalis were significant in the patients with surgery. In complicated UTIs without indwelling catheter, Klebsiella spp. was frequently isolated in the patients with surgery. In complicated UTIs with indwelling catheter, S. aureus and Staphylococcus spp. were frequently isolated in the patients without surgery.

Adolescent↗

[Pulmonary aspergilloma, diagnosis and treatment].

Pulmonary aspergilloma is a saprophytic form of aspergillosis, and the diagnosis is usually based on radiological findings such as thickened cavitary wall and fungus ball, and on positive serum antibody. Up to 58% of the patients with aspergilloma in Japan have medical history of tuberculosis. Serum anti-Aspergillus antigen is almost always positive in aspergilloma patients but aspergillus antigen is usually negative. Massive hemoptysis can be a fatal complication of aspergilloma, and the most common complication was respiratory failure according to our study. Surgical resection is the only promising intervention to cure the aspergilloma, however, low pulmonary function does not allow operation. Antifungal treatment is chosen for those who are out of operation indication, but the efficacy of antifungal treatment against aspergilloma is controversial. Some patients with aspergilloma show progressive form, and we define such aspergillosis as CNPA, chronic necrotizing aspergillosis, although the original entity of CNPA by Binder et al. is different. We make a diagnosis of CNPA only if all the following entity meets, 1; progressive shadows in radiological findings regardless of the presence of aspergilloma, 2; have some symptoms such as cough, sputum, hemosputum, hemoptysis or fever, 3; proof of Aspergillus attribution by mycological or pathological examination, 4; positive systemic inflammatory reaction, 5; neglect of other etiology of pulmonary diseases. Since CNPA is usually progressive, patients with CNPA should be treated with antifungals.

Aspergillosis↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2001). III. Secular changes in susceptibility].

The bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as urinary tract infections (UTIs) in 10 institutions in Japan were supplied between September and December, 2001. Then, the susceptibilities of these bacteria to various antimicrobial agents were examined, and the results were compared with those obtained between 1992 and 2000. Comparison was made by classifying strains isolated from patients into those in uncomplicated UTIs and those in complicated UTIs (including with or without indwelling catheter). The drug sensitivity of S. aureus in this year was comparable to those in up to the previous year, and S. aureus showed the best susceptibility to vancomycin (VCM). E. faecalis showed good susceptibility to ampicillin and imipenem, and the MIC90s were 2 micrograms/mL. The susceptibility of E. faecalis to VCM was also good. E. coli showed good susceptibility to the drugs except penicillins. Among cephems, the susceptibility to cefozopran (CZOP) was better (MIC90: < or = 0.125 microgram/mL). Just as the last report, the decreases in susceptibility of E. coli to quinolones were also observed in the patients with complicated UTIs. The susceptibility of Klebsiella spp. to all the test drugs did not significantly change in 2001 and was generally good but not to penicillins. Among cephems, Klebsiella spp. showed good susceptibility to flomoxef, cefpirome, cefixime, and CZOP with < or = 0.125 microgram/mL of MIC90s either in uncomplicated or complicated UTIs. Although the drug sensitivity of P. aeruginosa was generally low, the detection of the strains that showed good susceptibility to quinolones and carbapenems (MIC: < or = 0.125-2 micrograms/mL) were relatively frequent.

Anti-Bacterial Agents↗

Nepsilon-(Carboxymethyl)lysine induces gamma-glutamylcysteine synthetase in RAW264.7 cells.

Advanced glycation end products (AGEs) play an important role in the development of angiopathy in diabetes mellitus and atherosclerosis. Here, we show that adducts of N(epsilon)-(carboxymethyl)lysine (CML), a major AGE, and bovine serum albumin (CML-BSA) stimulated gamma-glutamylcysteine synthetase (gamma-GCS), which is a key enzyme of glutathione (GSH) synthesis, in RAW264.7 mouse macrophage-like cells. CML-BSA stimulated the expression of gamma-GCS heavy subunit (h) time- and dose-dependently and concomitantly increased GSH levels. CML-BSA also stimulated DNA-binding activity of activator protein-1 (AP-1) within 3h, but the stimulatory effect decreased in 5h, and nuclear factor-kappaB (NF-kappaB) with a peak activity at 1h and the stimulatory effect diminished in 3h. Studies of luciferase activity of the gamma-GCSh promoter showed that deletion and mutagenesis of the AP-1-site abolished CML-BSA-induced up-regulation, while that of NF-kappaB-site did not affect CML-BSA-induced activity. CML-BSA also stimulated the activity of protein kinase C, Ras/Raf-1, and MEK/ERK1/2. Inhibition of ERK1/2 abolished CML-BSA-stimulated AP-1 DNA-binding activity and gamma-GCSh mRNA expression. Our results suggest that induction of gamma-GCS by CML adducts seems to increase the defense potential of cells against oxidative stress produced during glycation processes.

Animals↗

Multidrug efflux systems play an important role in the invasiveness of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an important opportunistic human pathogen. Certain strains can transmigrate across epithelial cells, and their invasive phenotype is correlated with capacity to cause invasive human disease and fatal septicemia in mice. Four multidrug efflux systems have been described in P. aeruginosa, however, their contribution to virulence is unclear. To clarify the role of efflux systems in invasiveness, P. aeruginosa PAO1 wild-type (WT) and its efflux mutants were evaluated in a Madin-Darby canine kidney (MDCK) epithelial cell monolayer system and in a murine model of endogenous septicemia. All efflux mutants except a deltamexCD-oprJ deletion demonstrated significantly reduced invasiveness compared with WT. In particular, a deltamexAB-oprM deletion strain was compromised in its capacity to invade or transmigrate across MDCK cells, and could not kill mice, in contrast to WT which was highly invasive (P < 0.0006) and caused fatal infection (P < 0.0001). The other mutants, including deltamexB and deltamexXY mutants, were intermediate between WT and the deltamexAB-oprM mutant in invasiveness and murine virulence. Invasiveness was restored to the deltamexAB-oprM mutant by complementation with mexAB-oprM or by addition of culture supernatant from MDCK cells infected with WT. We conclude that the P. aeruginosa MexAB-OprM efflux system exports virulence determinants that contribute to bacterial virulence.

Animals↗

Helicobacter pylori infection in patients with gastric involvement by adult T-cell leukemia/lymphoma.

BACKGROUND: Gastrointestinal involvement is seen frequently in patients with adult T-cell leukemia/lymphoma (ATLL). The authors previously showed a relatively low prevalence of Helicobacter pylori infection in individuals with human T-cell lymphotropic virus 1 (HTLV-1) infection, including patients with ATLL; however, the correlation between H. pylori infection and ATLL gastric involvement has not been investigated. METHODS: The authors studied 71 patients with ATLL. Gastric involvement was confirmed by endoscopy and biopsy. H. pylori infection was detected by serology, rapid urease test, and immunohistochemistry on biopsy samples. The expression of adhesion molecules on ATLL cells or their ligands on the vasculature in gastric mucosa was analyzed immunohistochemically. The expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. RESULTS: Gastric involvement was detected in 21 patients (30%), including 8 patients with acute clinical subtype ATLL and 13 patients with lymphoma type ATLL. The prevalence of H. pylori infection was 86% (18 of 21 patients) in the patients with gastric involvement but only 38% (19 of 50 patients) in the patients without such involvement (P < 0.001). The expression of lymphocyte function-associated antigen 1 (LFA-1) and its ligand, intercellular adhesion molecule 1 (ICAM-1), was most frequent on ATLL cells infiltrating the stomach and was enhanced substantially on vascular endothelium in H. pylori-infected gastric mucosa. Human mucosal lymphocyte antigen 1 also was expressed on infiltrating ATLL cells in the stomach. The expression of MAdCAM-1 mRNA assessed by RT-PCR also was seen selectively in H. pylori-infected patients. CONCLUSIONS: ATLL cells infiltrate gastric tissues infected with H. pylori, probably through the interaction of adhesion molecules on these cells and their ligands on the vasculature, i.e., through the LFA-1/ICAM-1 pathway.

Adult↗

Histone deacetylase inhibitors suppress telomerase reverse transcriptase mRNA expression in prostate cancer cells.

Telomerase activity is involved in cellular immortality. We have recently demonstrated that telomerase activity is closely associated with cell proliferation in prostate cancers. Telomerase is composed primarily of the catalytic subunit (hTERT) and the RNA template (hTERC), and hTERT expression is regulated by several factors such as c-MYC and p21(Waf1). Histone deacetylase (HDAC) inhibitors are known to modulate transcription and exhibit antiproliferative effects on cancer cells. The present study was designed to evaluate the effects of HDAC inhibitors on hTERT mRNA expression in prostate cancer cells. LNCaP and PC-3 cells were treated with HDAC inhibitors, trichostatin A (TSA) and sodium butyrate (NaB); mRNA expression and telomerase activity were evaluated by RT-PCR and the TRAP assay, respectively. In LNCaP cells, hTERT mRNA expression was suppressed at 1 and 3 hr after treatment with 1 microM TSA and 4 mM NaB, respectively, followed by inhibition of telomerase activity. The inhibition of hTERT mRNA expression preceded suppression of cell proliferation. In PC-3 cells, TSA and NaB also inhibited cell proliferation, hTERT mRNA expression and telomerase activity. In both cell lines, TSA and NaB had no effect on hTERC expression, or on expression of c-myc and p21(Waf1) mRNA. These effects of TSA and NaB were unlikely to be consequences of cell cycle arrest, apoptosis, or cell differentiation. Thus, HDAC inhibitors down-regulated telomerase activity via suppression of hTERT mRNA expression. Our study identified a novel mechanism for the antiproliferative effects of HDAC inhibitors on prostate cancer cells.

Butyrates↗

Ulcerative colitis complicating pseudomembranous colitis of the right colon.

A 65-year-old man in the remission stage of ulcerative colitis developed severe bloody diarrhea and high fever. He was treated with imipenem/cilastatin and clindamycin for infectious enterocolitis at a local hospital, but there was no improvement in his condition. Steroid pulse therapy was also ineffective. Colonoscopy revealed pseudomembranous colitis extending from the ascending colon to the cecum, and Clostridium difficile toxin was positive in the feces. The administration of vancomycin in addition to oral steroids resulted in rapid improvement of the condition. Total colonoscopy is recommended for precise diagnosis when patients with ulcerative colitis develop intractable diarrhea during or after antibiotic therapy.

Anti-Bacterial Agents↗

Influence of Helicobacter pylori infection on in vitro responsiveness of gastric fundus to agonists and to stimulation of enteric nerves in Mongolian gerbils.

BACKGROUND: It has recently been proposed that disturbed gastric adaptive relaxation may play a role in functional dyspepsia (FD). However, the effect of Helicobacter pylori infection, which may be one of multiple factors associated with FD, on gastric relaxation is not clear. The aim of this study was to clarify the influence of H. pylori infection on the responsiveness of smooth muscles of the gastric fundus to agonists or to stimulation of enteric nerves, with particular emphasis on nonadrenergic noncholinergic (NANC) relaxation. METHODS: We investigated myogenic responses to carbachol (CCH) and sodium nitroprusside (SNP), and neural responses to electrical field stimulation (EFS), in the absence or presence of atropine and guanethidine, in the tissues of the gastric fundus of H. pylori-infected Mongolian gerbils (MGs). RESULTS: H. pylori-infected MGs showed typical gastritis, with H. pylori colonization in the antrum and body. The gastric fundus adjacent to the body was composed of thin gastric mucosa with mild inflammation, which was covered with stratified squamous epithelium, and the muscle layer communicated with that of the gastric body. In the gastric fundus, CCH- and SNP-induced responses were not different in controls and H. pylori-infected MGs. In the absence of any antagonists, EFS-evoked contraction tended to be reduced in H. pylori-infected MGs compared with that in control MGs, albeit that the difference was statistically nonsignificant. N(omega)-nitro- l-arginine methyl ester inhibited NANC relaxation in the tissues in both groups. EFS-evoked NANC relaxation remained intact in H. pylori-infected MGs. CONCLUSIONS: Mild inflammation in gastric fundus associated with H. pylori infection does not cause enteric neuromuscular dysfunction of the site in vitro.

Animals↗

Present status of hepatitis virus-associated hepatocellular carcinoma in Nagasaki Prefecture, Japan: a cross-sectional study of 1019 patients.

The present study was designed to determine the frequency of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in patients with hepatocellular carcinoma (HCC) in Nagasaki Prefecture, Japan. We examined the clinical features of 1019 patients with HCC who visited our hospitals between January and December 1999. The ratio of men to women was 709 : 310, and the peak incidence of HCC was in the seventh decade of life in both men and women. In the majority of the patients, HCC showed association with HCV infection (74%) compared with HBV infection (17%). HBV-associated HCC was more common in young patients, while HCV-associated HCC was more common in patients with a history as a "daily drinker", or with a history of blood transfusion, liver cirrhosis, and persistently high serum transaminases before the diagnosis of HCC. HCC was initially suspected by ultrasonography or computed tomography in 776 of the 874 patients for whom there was a history of mode of detection of HCC (89%). Tumor size at the time of diagnosis of HCC in patients who had been regularly followed up for liver diseases at our hospitals was significantly smaller than that in patients who were not followed up regularly before the diagnosis ( P < 0.01). Our results indicate that the proportions of patients with HBV or with HCV infection among HCC patients in Nagasaki Prefecture are similar to those found in a nationwide survey in Japan, and there are some differences between the clinical manifestations of HBV- and HCV-associated HCC. Our results emphasize the importance of close follow-up for the high-risk group (i.e. those with HBV- or HCV-associated chronic liver diseases) for the early detection of HCC.

Adult↗

Mutational analysis of the beta-tubulin gene in lung cancer.

Recently, several studies have suggested that a major mechanism of resistance to paclitaxel might involve mutations in the beta-tubulin gene in tumor cells. To investigate the frequency of beta-tubulin mutations in Japanese patients with small and non-small cell lung cancer, direct sequence analysis following reverse transcription-polymerase chain reaction (RT-PCR) of the beta-tubulin gene was performed using total RNA from 20 lung cancer cell lines and 22 specimens from lung cancer patients. First-strand cDNA sequence analysis of the 42 samples showed silent mutations at codon 180 of the beta-tubulin gene, which encodes the GTP-binding site of the protein, and codons 195 and 217. However, neither missense nor non-sense mutations affecting microtubule dynamics, within or near the GTP-binding site of the beta-tubulin gene, were detected. These results indicate that beta-tubulin gene mutations might not play a major role in the mechanism of resistance to paclitaxel in Japanese lung cancer patients. Further investigations are needed to clarify the mechanism of drug resistance.

Biopsy↗