[Evaluation of a new compact prothrombin time-international normalized ratio measurement device in pediatric management].

BACKGROUND: In a pediatric setting, the need for lifetime oral anticoagulation is increasing because of currency of extracardiac total cavo-pulmonary connection (TCPC) and pediatric valve surgery. We evaluated a new compact device "CoaguChek XS" for measuring prothrombin time-internatinal normalized ratio (PT-INR). METHODS: The international normalized ratio (INR) values obtained from 71 patients (223 samples) by a CoaguChek XS were compared with those obtained by a laboratory-based coagulation analyzer. RESULTS: The values from the CoaguChek XS had a significant correlation with the laboratory based results. (r2 = 0.92, p < 0.01, regression line y = 1.05 x -0.02). CONCLUSION: The CoaguChek XS will be useful in pediatric management.

[Senning operation for transposition of great arteries in a premature baby].

A male baby was delivered by emergency cesarean section due to fetal distress at 30 weeks of gestational age with a birth weight of 813 g. By fetal echocardiography, the patient had been diagnosed with transposition of great arteries (type 1). Early two-staged arterial switch operation was planned after 34 gestational age avoiding intracranial hemorrhage under cardiopulmonary bypass. At 19 days of life, vegetation was revealed on the pulmonary valve by echocardiography, so he was diagnosed as infectious endocarditis. Cefotaxime and gamma-globulin were given intravenously for 4 weeks. While waiting for the increase in the body weight, desaturation from chronic respiratory distress syndrome was exacerbated. At 8 months old, urgent Senning operation was performed to improve desaturation. The patient was discharged at 20 post operative day. We conclude that Senning operation can be feasible operation in such a complicated case.

Spontaneous loss of heterozygosity in diploid Saccharomyces cerevisiae cells.

To obtain a broad perspective of the events leading to spontaneous loss of heterozygosity (LOH), we have characterized the genetic alterations that functionally inactivated the URA3 marker hemizygously or heterozygously situated either on chromosome III or chromosome V in diploid Saccharomyces cerevisiae cells. Analysis of chromosome structure in a large number of LOH clones by pulsed-field gel electrophoresis and PCR showed that chromosome loss, allelic recombination, and chromosome aberration were the major classes of genetic alterations leading to LOH. The frequencies of chromosome loss and chromosome aberration were significantly affected when the marker was located in different chromosomes, suggesting that chromosome-specific elements may affect the processes that led to these alterations. Aberrant-sized chromosomes were detected readily in approximately 8% of LOH events when the URA3 marker was placed in chromosome III. Molecular mechanisms underlying the chromosome aberrations were further investigated by studying the fate of two other genetic markers on chromosome III. Chromosome aberration caused by intrachromosomal rearrangements was predominantly due to a deletion between the MAT and HMR loci that occurred at a frequency of 3.1 x 10(-6). Another type of chromosome aberration, which occurred at a frequency slightly higher than that of the intrachromosomal deletion, appeared to be caused by interchromosomal rearrangement, including unequal crossing over between homologous chromatids and translocation with another chromosome.

[The indications for autonomic nerve-sparing surgery in rectal cancer patients].

Although extended lymph node dissection was developed to improve the therapeutic result in advanced rectal cancer in the 1970s, postoperative dysfunction remained problematic. Informed consent of cancer is generalized at present. The balance between complete cure and functional preservation is important. Therefore the autonomic nerve-sparing surgical technique for rectal cancer was introduce din the 1980s. The success of nerve-sparing surgery depends on a thorough knowledge of pelvic anatomy, especially the anatomic relationship between the pelvic plexus and internal intestinal vessels. Further investigation is required to clarify the indications for autonomic nerve-sparing surgery in rectal cancer patients.

[A comparative study on the clinical utility of cefozopran and cefpirome against complicated urinary tract infections].

Aiming at evaluating the utility of cefozopran (CZOP) against complicated urinary tract infections with the velocity of eradication of causal bacteria in early treatment and clinical efficacy by new criteria of UTIs, a comparative study was conducted using cefpirome (CPR) as the control drug. CZOP and CPR were administered by intravenous drip infusion at a dose of 1 g twice daily. The duration of treatment was for 5 days. The study method involved randomized assignment of the subjects to either group CZOP or group CPR. The results were as follows: 1. Of a total of 80 cases treated, 65 (CZOP group--32 cases, CPR group--33 cases) were evaluated for efficacy. 2. The overall clinical efficacy evaluation according to the criteria proposed by Japanese UTI Committee rated the CZOP group as 90.6% (29/32), and the CPR group as 90.9% (30/33), with no significant difference between the 2 groups. Clinical efficacy evaluated by attending physicians rated the CZOP group as 93.8% (30/32) and the CPR group as 90.9% (30/33). There was no significant difference between the 2 groups. 3. The efficacy rates to pyuria on day 2 were 26.7% and 0% for the CZOP group and the CPR group, respectively, indicating a higher efficacy rate for the former (p < 0.05). Those on after treatment were 59.4% and 54.5% for the CZOP group and the CPR group, respectively, with no significant difference between the 2 groups. 4. Regarding the bacteriological effect, the eradication rates of both groups were over 90% on day 1 and after treatment. There was no significant difference between the 2 groups. 5. Side effects occurred in 1 case (2.6%) out of 39 in the CZOP group and in 1 case (2.4%) out of 41 in the CPR group. Laboratory test value fluctuation was noted in 8 (20.5%) of 39 cases in the CZOP group and 11 (26.8%) of 41 cases in the CPR group. There was no significant difference between the 2 groups. The results indicate that CZOP achieves an early efficacy to pyuria, and is as useful as CPR against complicated urinary tract infections.

Chromosomal rearrangements occur in S. cerevisiae rfa1 mutator mutants due to mutagenic lesions processed by double-strand-break repair.

Three temperature-sensitive S. cerevisiae RFA1 alleles were found to cause elevated mutation rates. These mutator phenotypes resulted from the accumulation of base substitutions, frameshifts, gross deletions (8 bp-18 kb), and nonreciprocal translocations. A representative rfa1 mutation exhibited a growth defect in conjunction with rad51, rad52, or rad10 mutations, suggesting an accumulation of double-strand breaks. rad10 and rad52 mutations eliminated deletion and translocation formation, whereas a rad51 mutation increased the frequency of these events and revealed a new class of genetic rearrangements--loss of a portion of a chromosome arm combined with telomere addition. The breakpoints of the translocations and deletions were flanked by imperfect direct repeats of 2-20 bp, similar to the breakpoint structures observed at translocations and gross deletions, including LOH events, underlying human cancer and other hereditary diseases.

Saccharomyces Ku70, mre11/rad50 and RPA proteins regulate adaptation to G2/M arrest after DNA damage.

Saccharomyces cells suffering a single unrepairable double-strand break (DSB) exhibit a long, but transient arrest at G2/M. hdf1 cells, lacking Ku70p, fail to escape from this RAD9/RAD17-dependent checkpoint. The effect of hdf1 results from its accelerated 5' to 3' degradation of the broken chromosome. Permanent arrest in hdf1 cells is suppressed by rad50 or mre11 deletions that retard this degradation. Wild-type HDF1 cells also become permanently arrested when they experience two unrepairable DSBs. Both DSB-induced arrest conditions are suppressed by a mutation in the single-strand binding protein, RPA. We suggest that escape from the DNA damage-induced G2/M checkpoint depends on the extent of ssDNA created at broken chromosome ends. RPA appears to play a key intermediate step in this adaptation.

Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism.

Replication protein A (RPA) is a single-stranded DNA-binding protein identified as an essential factor for SV40 DNA replication in vitro. To understand the in vivo functions of RPA, we mutagenized the Saccharomyces cerevisiae RFA1 gene and identified 19 ultraviolet light (UV) irradiation- and methyl methane sulfonate (MMS)-sensitive mutants and 5 temperature-sensitive mutants. The UV- and MMS-sensitive mutants showed up to 10(4) to 10(5) times increased sensitivity to these agents. Some of the UV- and MMS-sensitive mutants were killed by an HO-induced double-strand break at MAT. Physical analysis of recombination in one UV- and MMS-sensitive rfa1 mutant demonstrated that it was defective for mating type switching and single-strand annealing recombination. Two temperature-sensitive mutants were characterized in detail, and at the restrictive temperature were found to have an arrest phenotype and DNA content indicative of incomplete DNA replication. DNA sequence analysis indicated that most of the mutations altered amino acids that were conserved between yeast, human, and Xenopus RPA1. Taken together, we conclude that RPA1 has multiple roles in vivo and functions in DNA replication, repair, and recombination, like the single-stranded DNA-binding proteins of bacteria and phages.

[Uretero-external iliac artery fistula: a case report].

We report a case of uretero-external iliac artery fistula. A 60-year-old female was referred to our hospital complaining of intermittent gross macrohematuria. She had undergone radical hysterectomy, radiation therapy and chemotherapy for advanced cervical cancer 2 years ago. The patient had a 7 Fr ureteral double-J stent for left hydronephrosis. Retrograde urography showed a filling defect (8 mm in diameter) of the left ureter. A contrast-enhanced computed tomographic scan showed left hydronephrosis and hydroureter but no evidence of fistula formation or extravasation. A pelvic arteriography revealed a pseudoaneurysm of the left external iliac artery at the crosspoint between the left ureter and the iliac artery. Surgical repair of the left uretero-external arterial fistula was successfully performed as well as left nephroureterectomy. The possibility of fistula formation between ureter and artery should be kept in mind in patients with long-term indwelling ureteral stents and history of radiation therapy.

Computerized Image Analysis of Clustered Microcalcifications on Mammography: Morphome- tric Comparison between Mammography and Pathology.

The clusters of microcalcifications under 2 cm in greatest dimension were analyzed in terms of size and shape by an image processor with a computer after being magnified 33 times. The mean diameter of mammographic microcalcifications was 188 µ m in benign cases, 226µ m in cribriform or papillary type cancer cases, 213 µ m in intermediate type cancer cases, and 324µ m in comedo type cancer cases, showing significant differences among the groups. The size distribution of mammographic microcalcifications in the comedo type was characteristic, showing a second peak in distribution between 500 and 700µ m. The radiodensity of microcalcifications compared to the breast parenchyma, the caliber of breast ducts containing the malignant calcifications, and the unit volume of calcium deposits within the ductal lumens were greater in cancer cases. The size and shape of mammographic microcalcifications were considered to be related to a combination of the caliber of breast ducts, unit volume of calcium deposits within the ductal lumens, and the density of breast ducts containing calcium deposits. Duct calibers were generally larger in cases of cancer lesions than cases of benign lesions such as duct papillomatosis, thus calcium deposits and microcalcifications were greater in the cancer lesion. Uneven distrubution of size and form of microcalcifications over 250 µ m in size, and increased radiodensity of calcifications were useful parameters for differential diagnosis rather than the density of calcifications.

[Vesicouterine fistula: a case report].

A 25-year-old woman suffered a vesicouterine fistula following cesarean section. Cystoscopic fulguration of the fistula was attempted, resulting in disappearance of incontinence. Two months later, incontinence recurred and open surgical repair was performed transabdominally. After resection and closure of the fistula with the help of peritoneal flap interposition, the patient became free from incontinence.

[A case of renal cell carcinoma with an extremely high serum carcinoembryonic antigen level].

A case of renal cell carcinoma with extremely high serum carcinoembryonic antigen (CEA) levels is presented. A 57-year-old female complained of left flank pain. Computerized tomographic (CT) scan revealed left renal tumor and laboratory examination revealed an extremely high serum level of CEA (815 ng/ml). No abnormal findings were recognized in gastrointestinal or genital systems. Radical nephrectomy was done. The histology was renal cell carcinoma (RCC, intermediate type, mixed type, pleomorphic cell type, G3 > G2, INF gamma, pT2, pV0). Tumor cells were positive for CEA by ABC-peroxidase staining. Levels of tumor markers decreased after operation. However, CEA levels rose again and lymph node metastases appeared. She died 6 months after operation.

[Tuberculous spondylitis after intravesical BCG instillation: a case report].

We report a case of tuberculous spondylitis after intravesical bacillus Calmette-Guerin (BCG) instillation. A 71-year-old man was administered BCG (80 mg per week) for 8 weeks for prophylactic treatment of bladder cancer. After the first instillation he experienced miction pain, pollakisuria, and febrile episodes. Two months after the completion of BCG instillation, he complained to back pain and spinal X-ray showed a lytic lesion of Th7 vertebra. Diagnosis of metastatic transitional cell carcinoma was made based on MRI and bone scan. But pathological findings at laminectomy revealed tuberculous spondylitis. Antituberculous therapy (SM, RFP, and INH) was instituted and anterior supine fusion was performed. Now he is free from bladder cancer and tuberculous infection. Intravesical BCG instillation is effective for superficial bladder cancer, but it should be kept in mind that complications related to this treatment could occur and the adequate antituberculosis treatment has to be insisted if indicated.

Hepatocyte growth factor stimulates liver regeneration and elevates blood protein level in normal and partially hepatectomized rats.

The effects of recombinant human hepatocyte growth factor (HGF) on liver growth and function of normal and partially hepatectomized rats have been examined. HGF was continuously administered into the jugular vein because it was rapidly eliminated from the plasma (t1/2 alpha; approximately 4.5 min) and degraded. In normal rats, the labeling index of hepatocytes was increased about 6 times by the administration of HGF. HGF also decreased the prothrombin time and increased the hepaplastin and serum albumin content. In 70%-hepatectomized rats, HGF stimulated liver regeneration and increased the level of blood proteins such as hepaplastin in a dose-dependent manner. The stimulation of serum protein level seemed to result from not only the increase of hepatic cell number but also the direct effect of HGF on the protein production in hepatocytes, because HGF rapidly enhanced the protein synthesis prior to the increase of cell number and increased the mRNA content of albumin in the liver in vivo. In addition, a combination of heparin with HGF further accelerated the effects of HGF described above, possibly due to the decrease of HGF clearance. These findings suggest that HGF accelerates both the hepatic regeneration and function in vivo, and that rhHGF is clinically expected to be a potent therapeutic agent in hepatectomy and liver injury.

[Bilateral testicular Leydig cell tumor with adrenocortical adenoma: a case report].

A case of bilateral testicular Leydig cell tumor with left adrenocortical adenoma in a 27-year-old male is presented. He underwent bilateral radical orchiectomy, and was diagnosed with a malignant Leydig cell tumor. Computed tomography revealed left adrenal mass and primary adrenal tumor or metastatic malignant Leydig cell tumor was suspected. Left adrenalectomy was performed and the histopathological diagnosis was adrenal cortical adenoma. The adrenal cortex and testicle are of common mesodermal origin and the histologic pattern may overlap. Examination of the adrenal gland is necessary for patients with testicular Leydig cell tumor. We review and briefly discuss a case recently reported in Japan.

Effect of a major metabolite of the antiallergic drug repirinast on phosphodiesterase and adenylate cyclase activities.

MY-1250 (5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c]quinoline-2-carboxylic acid, CAS 63768-47-8), a major metabolite of the antiallergic drug repirinast (MY-5116, CAS 73080-51-0), inhibits antigen-induced histamine release from rat peritoneal mast cells. MY-1250 causes a rapid increase in cyclic adenosine monophosphate (AMP) levels in rat peritoneal mast cells. MY-1250 inhibited cyclic AMP phosphodiesterase activities from rat peritoneal cells and guinea pig lung tissue in a concentration dependent manner with IC50 values of 2000 mumol/l and 1670 mumol/l, respectively. However, MY-1250 showed no effect on adenylate cyclase activity from rat peritoneal cells. These results suggest that the inhibitory effect of MY-1250 on histamine release may be partly due to the inhibition of cyclic AMP phosphodiesterase activity.

Protein interactions in genetic recombination in Escherichia coli. Interactions involving RecO and RecR overcome the inhibition of RecA by single-stranded DNA-binding protein.

RecA promotes homologous pairing of single-stranded DNA (ssDNA) with double-stranded DNA (dsDNA). This reaction occurs inefficiently if the ssDNA substrate is preincubated with Escherichia coli ssDNA-binding protein (SSB). However, RecO and RecR can act together as accessory factors for RecA to overcome this inhibition by SSB (Umezu, K., Chi, N.-W., and Kolodner, R. D. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 3875-3879). To elucidate the mechanism that underlies this process, we examined protein-protein interactions between RecA, RecF, RecO, RecR, and SSB, and characterized the structure and activity of the ssDNA complexes formed with different combinations of these proteins. We obtained the following results. (i) RecO physically interacts with both RecR and SSB. The interaction between RecO and SSB is stronger than the RecO-RecR interaction. (ii) RecO and RecR do not remove SSB from SSB.ssDNA complexes, but instead bind to these complexes. The resulting RecO.RecR.SSB.ssDNA complexes were more active in RecA-mediated joint molecule formation than were SSB.ssDNA complexes. (iii) RecA can nucleate on the RecO.RecR.SSB.ssDNA complexes more efficiently than on SSB.ssDNA complexes. (iv) When RecA presynaptic filaments were formed in the presence of SSB, RecO, and RecR, the protein-DNA complexes obtained contained 70% of the amount of RecA required to saturate ssDNA. These complexes, however, can mediate joint molecule formation and strand exchange as efficiently as presynaptic filaments which are fully saturated with RecA. Based on these results, we propose dual roles for RecO and RecR in joint molecule formation. First, RecO and RecR bind to SSB.ssDNA complexes and modify their structure to allow RecA to nucleate on them efficiently. Second, RecO and RecR are retained in RecA presynaptic filaments and play a role in the subsequent homologous pairing process promoted by RecA.

Pharmacological profile of the novel, potent and selective peptide leukotriene antagonist (E)-2,2-diethyl-3'-[2-[2-(4-isopropyl)thiazolyl]ethenyl]succinanilic acid.

In this report, the in vitro and in vivo pharmacological profile of MCI-826 ((E)-2,2-diethyl-3'-[2-[2-(4-isopropyl) thiazolyl]ethenyl]succinanilic acid, CAS 121230-22-6) is described. In isolated guinea pig ileum, MCI-826 inhibited LTD4 (a peptide leukotriene, 10(-9) mol/l)-induced contraction in a concentration-dependent manner with an IC50 of 6.8 x 10(-12) mol/l. It had no effect on histamine (10(-5) mol/l)-, serotonin (2.5 x 10(-5) mol/l)-, or acetylcholine (5.5 x 10(-6) mol/l)- induced contractions in isolated guinea pig ileum. In isolated guinea pig trachea, MCI-826 demonstrated competitive antagonism of the contractile activity of LTD4 and LTE4 with pA2 values of 9.0 and 8.8, respectively. MCI-826 inhibited LTC4-induced contraction in a concentration-dependent manner. However, in the presence of an inhibitor of the metabolism of LTC4 to LTD4, MCI-826 (10(-6) mol/l) produced no effect on LTC4 concentration-response curves in guinea pig trachea. In the in vivo study, the oral administration of MCI-826 caused a dose-dependent inhibition of LTC4- and LTD4-induced bronchoconstrictions in guinea pigs with an ED50 of 0.049 and 0.013 mg/kg, respectively. However, MCI-826 (3 mg/kg p.o.) showed no effect on histamine-induced bronchoconstriction in guinea pigs. The pharmacological half-life of orally administered MCI-826 as assessed by LTD4-induced bronchoconstriction was more than 12 h in guinea pigs. MCI-826 also inhibited antigen-induced bronchoconstriction in a dose-dependent manner with a MID (minimum dose that causes significant inhibition) of 0.1 mg/kg p.o. in guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Syntheses and pharmacological activities of novel optically active inhibitors of acyl-CoA: cholesterol O-acyltransferase: EAB-309 ((R)-N-2-(1,3-benzodioxol-4-yl)heptyl-N'-2,6-diisopropylphenylurea) and its enantiomer.

Novel and potent ACAT (acyl-CoA: cholesterol O-acyltransferase) inhibitors, (R)-N-2-(1,3-benzodioxol-4-yl)heptyl-N'-2,6-diisopropylphenylur ea (2a, EAB-309), and its enantiomer 2b (EAB-310), were prepared from 4-(1,3-benzodioxole)carbaldehyde (7) via optically active (R or S)-2-(1,3- benzodioxol-4-yl)heptanoic acid (12a or 12b). Compound 2a showed potent inhibitory effects on ACATs in vitro, and lowered plasma cholesterol in vivo. The IC50 value for inhibition of rat hepatic microsomal ACAT was 5 nM. The ED30 values of hypolipidemic activities in hamster and rat models were 0.25 and 0.75 mg/kg p.o., respectively. The results indicate that 2a has potential to be a novel hypocholesterolemic and antiatherosclerotic agent. The activities of 2a in vitro and in vivo were only several times more potent than those of the enantiomer 2b. Modeling studies suggested that the three-dimensional structures of the two enantiomers are similar to each other.