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To identify amplified oncogenes involved in hepatocellular carcinomas (HCC), we applied a genomic DNA microarray spotted with 57 oncogenes to 20 HCCs. Aberrations in DNA copy number also were analyzed by comparative genomic hybridization (CGH) using an aliquot of DNA samples. In 5 of 20 HCCs, only 6 oncogenes (CCND1, FGF3/FGF4, SAS/CDK4, TERC, MET, and MYC) were amplified, whereas in the remaining 15 tumors no oncogenes were amplified. A comparison of DNA microarray and conventional CGH analyses showed that, although 5 of 6 amplified oncogenes shown by microarray were located in chromosomal regions shown by CGH to have increased DNA copy numbers, not all genes located in such chromosomal regions were affected. One of the amplified oncogenes (SAS/CDK4) was found in a chromosomal region that was undetected by CGH. We, therefore, conclude that amplification of the oncogenes examined in this series is not directly implicated in hepatocellular carcinogenesis.

We used a rabbit model to test the postoperative mechanical strengths of two new tendon suture techniques. These were compared with the conventional modified Kessler and double looped suture techniques. For each technique, maximum load until 3 mm gap, load at 1 mm gap and ultimate load were measured at the time of operation and at weeks 1 and 3 after operation.Maximum load until 3 mm gap and load at 1 mm gap were significantly higher in the new techniques than in the conventional techniques at the time of operation and at 1 week; there was no statistical difference between the four techniques at 3 weeks. No technique resulted in a decrease in maximum load until 3 mm gap, load at 1 mm gap and ultimate load at 1 week.The new techniques reported here have the potential to withstand early active flexion exercises.

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In 16 institutions around the entire Japan, 557 strains of presumably etiological bacteria were isolated mainly from the sputa of 449 patients with lower respiratory tract infections during the period from October 1996 to September 1997. MICs of various antibacterial agents and antibiotics were determined against 98 strains of Staphylococcus aureus, 93 strains of Streptococcus pneumoniae, 84 strains of Haemophilus influenzae, 84 strains of Pseudomonas aeruginosa (non-mucoid strains), 17 strains of Pseudomonas aeruginosa (mucoid strains), 31 strains of Moraxella subgenus Branhamella catarrhalis, 21 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were assessed except for those strains that died during transportation. 1) S. aureus S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 67.3%. The frequency of the drug resistant bacteria increased comparing to the previous year's 52.7%. Arbekacin (ABK) and vancomycin (VCM) showed the highest activities against both S. aureus and MRSA with MIC80s of 1 microgram/ml. 2) S. pneumoniae Imipenem (IPM) and panipenem (PAPM) of carbapenems showed the most potent activities with MIC80s of 0.063 microgram/ml. Faropenem (FRPM) showed the next potent activity with MIC80 of 0.125 microgram/ml. The other drugs except erythromycin (EM), clindamycin (CLDM) and tetracycline (TC) were active against S. pneumoniae tested with MIC80s of 8 micrograms/ml or below. 3) H. influenzae The activities of all drugs were potent against H. influenzae tested with MIC80s of 4 micrograms/ml or below. Cefotiam (CTM), cefmenoxime (CMX), cefditoren (CDTR) and ofloxacin (OFLX) showed the most potent activities with MIC80s of 0.063 microgram/ml. 4) P. aeruginosa (mucoid strains) Tobramycin (TOB) showed the most potent activity against P. aeruginosa (mucoid strains) with MIC80 of 1 microgram/ml. Ceftazidime (CAZ), cefsulodin (CFS), IPM, gentamicin (GM), ABK and ciprofloxacin (CPFX) showed the next potent activities, with MIC80s of 2 micrograms/ml. The MIC80s of the other drugs ranged from 4 micrograms/ml to 16 micrograms/ml. 5) P. aeruginosa (non-mucoid strains) TOB and CPFX showed the most potent activities against P. aeruginosa (non-mucoid strains) with MIC80s of 1 microgram/ml. The MIC80s of piperacillin (PIPC) and cefoperazone (CPZ) were 16 micrograms/ml in 1995, and they were 64 micrograms/ml in 1996. 6) K. pneumoniae All drugs except ampicillin (ABPC) were active against K. pneumoniae. CMX, cefpirome (CPR), cefozopran (CZOP) and carumonam (CRMN) showed the most potent activities against K. pneumoniae with MIC80s of 0.125 microgram/ml. The MIC80s of the other drugs ranged from 0.25 microgram/ml to 2 micrograms/ml. 7) M.(B) catarrhalis Against M.(B.) catarrhalis, all drugs showed good activities with MICs of 4 micrograms/ml or below. IPM and minocycline (MINO) showed the most potent activities with MICs of 0.063 microgram/ml. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. Patients' backgrounds were examined for 557 isolates from 449 cases. The examination of age distribution indicated that the proportion of patients with ages over 60 years was 71.0% of all the patients showing a slight increase over that in 1994. Proportions of diagnosed diseases were as follows: Bacterial pneumonia and chronic bronchitis were the most frequent with 35.9% and 30.3% respectively. They were followed by bronchiectasis with a proportion of 10.

The pathogenicity of Streptococcus constellatus in pulmonary infections was investigated in mice in correlation with the phagocytic killing of the microorganisms by human polymorphonuclear neutrophils (PMNs). The histological inflammation score of the lungs in mice inoculated intratracheally with 10(8) cfu/mouse of the virulent strain S. constellatus RZYK001 obtained from bronchoalveolar fluid of a patient with pneumonia, was significantly higher than in mice inoculated with the avirulent strains S. constellatus RT4303 and RT6002 obtained from saliva of healthy adults (p0.001). The bactericidal activity of human PMNs against Staphylococcus aureus ATCC 25923 was not inhibited at all by the culture filtrate of the virulent strain, but the killing index against RZYK001 was 36.4% after 90-min incubation whereas that against RT4303 and RT6002 was 94.7% and 99.4%, respectively (p0.001). Therefore, these results suggest a possible pathogenic mechanism of S. constellatus apparently mediated by a structural component of the organisms so that a virulent strain is less likely to be killed than an avirulent one, predisposing it to survive in the infection sites.

We had examined antibody titers against Legionella spp. of patients' sera which were mainly sent from other hospitals, performed with the indirect fluorescent antibody (IFA) method. The clinical status of the cases diagnosed as Legionella pneumonia serologically, were also studied. Out of 105 cases with clinically suspected Legionella pneumonia, 15 cases (14.3%) were seropositive. In 9 out of the 15 cases (60.0%) were caused by Legionella pneumophila serogroup 1. Clinical outline of these 15 cases did not contradict those reported in the literature, and erythromycin was effective in many cases. Significant rises (more than four times) of the titer were observed 3 to 4 weeks after onset in most of cases. We would like to emphasize that this should be performed serodiagnosis of Legionella pneumonia.

The bacteriology of empyema fluid and the clinical background of 23 cases from July 1987 through July 1992 were studied. Nineteen cases were male and 4 female, with a mean age of 59.6 years (range; 33 to 84 y.o.). There were 15 cases of community-acquired infection and 8 of nosocomial infection. Acute pneumonia and/or lung abscess developed into empyema in 19 cases. Sixteen cases had associated predisposing conditions, such as diabetes, chronic bronchitis, disorders with dysphagia, and excess alcohol intake. Forty-one strains were isolated from empyema in 22 cases. The predominant organisms, in order of prevalence, were "Streptococcus milleri" group (11 strains), Peptostreptococcus spp. (6), Prevotella spp. (6), Fusobacterium spp. (5) and other viridans streptococci (3). The majority of streptococcal infections, which were primarily caused by "S. milleri" group, were mixed with anaerobes and/or aerobes/facultatives. These results demonstrate that oral streptococci, especially "S. milleri" group, and anaerobes play a significant role as pathogens in empyema.

Forty patients with chronic respiratory infections were randomly assigned to 2 groups to compare the effect of once daily administration of 300 mg each and 3 times daily administration of 600 mg each of ofloxacin (OFLX). Twenty patients were administered with 300 mg OFLX a day and 18 cases received 600 mg. The number of underlying diseases in the 300 mg group was greater than that in the 600 mg group. The ratios of general amelioration of clinical symptoms were 80.0% in the 300 mg group and 88.9% in the 600 mg group. For bacteriological effects, the eradication rate was 80.0% in the 300 mg group and it was 84.6% in the 600 mg. The incidence of side effects in the 300 mg group was 0% and that of the 600 mg group was 5.6% (1 patient) but the symptom was mild. The incidence of abnormal laboratory test results was 15.0% in the 300 mg group and it was 11.2% in the 600 mg group, but all of these abnormalities were slight and transient. The safety rates in the 300 mg and the 600 mg groups were 95.0% and 94.4%, respectively. Efficacy rates in the 300 mg and the 600 mg groups were 80.0% and 88.9%, respectively. There was no statistically significant difference in all the results between the 2 treatment groups, and the both treatments were highly effective. From the above results, we consider that once daily administration of 300 mg is a useful therapy in respiratory tract infections.

Fifty-two patients with moderate or severe infections associated with internal medicine were treated with imipenem/cilastatin sodium (IPM/CS) and the efficacy and the safety of this drug were evaluated. There were 20 patients with pneumonia, 10 with acute exacerbation of chronic respiratory tract infections, 9 with sepsis, 2 with pyothorax, 3 with intraabdominal infection, 2 with urinary tract infection, 1 with pulmonary abscess, 1 with infective endocarditis, 4 with fever of unknown origin. Forty-four patients were evaluable for the efficacy. Clinical efficacies were excellent in 12 patients, good in 26, fair in 3 and poor in 3. The overall clinical efficacy was 86.4%. The efficacy rate was 63.6% in patients previously treated and 93.9% in patients previously untreated with other antibiotics. Bacteriologically, Staphylococcus aureus (8 strains), Streptococcus pneumoniae (5), Streptococcus pyogenes (1), other Gram-positive coccus (1), Klebsiella pneumoniae (8), Haemophilus influenzae (4), Pseudomonas aeruginosa (3), Serratia marcescens (3), Escherichia coli (3), Branhamella catarrhalis (1), Citrobacter freundii (1), Klebsiella oxytoca (1), Enterobacter sp. (1), and Peptostreptococcus sp. (1) were eradicated. P. aeruginosa (3) and Acinetobacter sp. (1) decreased. S. aureus (1), S. epidermidis (1), P. aeruginosa (5), and S. marcescens (1) persisted or appeared. The eradication rate was 83.7%. Six patients showed adverse reactions including general fatigue 1, epigastralgia 1, eruption 1, eosinophilia 1 and elevation of S-GOT 2. But all of the adverse reactions were mild or slight, and transient. These findings indicate that IPM/CS is a useful and safe drug against bacterial infections in internal medicine.

Tuberculin purified protein derivative (PPD) is a relatively crude antigen prepared from Mycobacterium tuberculosis and has species nonspecificity in immunological reaction. It is, however, more readily available than more highly purified materials. Therefore, the detection of IgG antibody to PPD was done by enzymed-linked immunosorbent assay (ELISA) and its diagnostic useful was evaluated in this study. The patients with active tuberculosis had significantly high titer of IgG antibody to PPD compared with healthy persons and the patients without tuberculosis (P less than 0.001). An upper limit of normal set (=cut-off titer) at 2 standard deviations above mean of logarithmic titers in 220 healthy adult subjects would result in positive test reactions on the sera from 78 of 100 patients with active tuberculosis. Although 8 of 39 with atypical mycobacteriosis would be positive, 6 of 7 were distinguished almost with tuberculosis by detecting antibodies to PPD from M. intracellulare and M. kansasii concurrently. The antibody titer increased after chemotherapy would be gradually reduced under the cut-off titer when culture of mycobacteria turned to negative and markers of inflammation became negative. In false-negative cases, 4 were patients with hypo-gammaglobulinemia, 6 were with fresh tuberculosis before chemotherapy, 2 were with negative CRP in all clinical course and 4 were with bacilli needed over 7 weeks culture. From these results, this assay is helpful in the diagnosis of tuberculosis and a useful marker for judgment of clinical improvement, although detection of antibody has its limitations.

A case of severe head injury associated with fulminant pulmonary edema considered as neurogenic which developed within short time after the injury was presented. A five-year-old boy who had no previous history of cardiopulmonary disease was struck on his right frontal region by car accident at 15.30 PM on July 5 of 1979. Immediately after the impact he lost his consciousness and subsequently transferred to a local hospital where bilateral dilated pupil and flaccid paralysis of the limbs were noted. On transmission of the patient to Omuta City Hospital 30 minutes after the injury, massive foamy fluid was discharged from the tracheal tube. On admission, he was comatous, with bilateral dilated and fixed pupils and flaccid paralysis of the limbs. There was no retinal bleeding. He showed ataxic respiration with severe stridor and massive discharge of foamy fluid pinkish in colour from the trachea characteristic in pulmonary edema was significant. Chest x-ray film demonstrated perihilar densities suggesting pulmonary edema. CT scan showed extremely small ventricle on both sides without manifestations of intracranial hematomas or cerebral contusion. With an intensive medical treatments including corticosteroids, alkalizing agents and alpha-blocker were administered under controlled respiration, the discharge of edema fluid was gradually decreased and the findings on blood gases were also improved. However neurological signs were aggravated and he died 8 hours after the injury. Central venous pressure was maintained at the level between 8 to 10 cm. From these clinical findings the pulmonary edema was concluded as neurogenic. Direct or indirect injury to the hypothalamic efferent pathway at the level of lower brain stem seemed to be important as the cause of neurogenic pulmonary edema in this case. The possible pathophysiology of neurogenic pulmonary edema associated with brain stem injury and intracranial hypertension was discussed with other related literature.

Histopathological observations were made on the spontaneous age-related kidney lesion in relation to some biochemical measurements for renal function using male SD rats from 82 to 560 days of age. Although all the rats examined were appearently healthy and had no gross lesions in the kidneys, several renal changes were detected histopathologically in the kidneys. The lesions occurred initially in renal tubules and then in glomerulus and in interstitial tissues successively increasing in severity with age. There was a correlation between the degree of the histopatholigical changes and the excreted amount of protein and sodium in the urine. The urinary protein was first detected at 34 days of age increasing with age. For rats of over 395 days of age, the urinary protein was greatly variable in amount among individuals. The negative correlation between urinary protein levels and those of serum albumin and urinary potassium was significant.