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K Yamaguchi

Publications and source records attributed to K Yamaguchi.

At least 415 records · Page 23Linked to original sources
PubMed1999

Spectroscopic and electrochemical properties of two azurins (Az-iso1 and Az-iso2) from the obligate methylotroph Methylomonas sp. strain J and the structure of novel Az-iso2.

Two azurin-type blue copper proteins, which are related to the electron-transfer processes involving methylamine/methanol oxidation, have been spectroscopically and electrochemically characterized. The obligate methylotroph Methylomonas sp. strain J gives rise to two azurins (Az-isol and Az-iso2) with methylamine dehydrogenase (MADH-Mj). The intense blue bands characteristic of Az-iso1 and Az-iso2 are observed at 621 and 616 nm in the visible absorption spectra respectively, being revealed at 620-630 nm in those of usual azurins. The EPR signal of Az-iso1, similar to usual azurins, shows axial symmetry, while the axial EPR signal of Az-iso2 involves a slightly rhombic character. The half-wave potentials (E1/2) of the two azurins and the intermolecular electron-transfer rate constants (kET) from MADH-Mj to each azurin were determined by cyclic voltammetry. The E1/2 values of Az-iso1 and Az-iso2 are +321 and +278 mV vs NHE at pH 7.0, respectively. The kET value of Az-iso2 is larger than that of Az-iso1 by a factor of 5. However, the electron-transfer rate of Az-iso2 is interestingly slower than those of the azurins from a denitrifying bacterium, Alcaligenes xylosoxidans NCIB 11015, and the amicyanin from a different methylotroph, Methylobacterium extorquens AM1. The structure of Az-iso2 has been determined and refined against 1.6 A X-ray diffraction data. The whole structure of Az-iso2 is quite similar to those of azurins reported already. The Cu(II) site of Az-iso2 is a distorted trigonal bipyramidal geometry like those of other azurins, but some of the Cu-ligand distances and ligand-Cu-ligand bond angle parameters are slightly different. These findings suggest that Az-iso2 is a novel azurin and perhaps functions as an electron acceptor for MADH.

Azurin↗
PubMed1999

Negligible role of catecholaminergic receptors in the anteroventral third ventricular region in mediating vasopressin-releasing and cardiovascular actions of prostaglandin E2.

The aim of this study was to pursue the roles of the catecholamine receptors in the anteroventral third ventricular region (AV3V), a cerebral site engaged in various stress responses, in prostaglandin (PG) E2-evoked vasopressin (AVP) release and cardiovascular action. Experiments were conducted in conscious rats in which cerebral and vascular cannulae had been implanted chronically. Local infusion (0.5 microliter, 1 min) of dopamine (150 nmol), a D1-dopaminergic agonist SKF 38393 (17 nmol) and an alpha-adrenergic agonist phenylephrine (150 nmol), as well as PGE2 (7 nmol), into the AV3V enhanced plasma AVP 5 min later, without affecting plasma osmolality and electrolytes. In contrast to the increases in both arterial pressure and heart rate observed when PGE2 was applied, dopamine and SKF 38393 did not affect these variables, and phenylephrine elevated only arterial pressure. The AV3V infusion of a beta-agonist isoproterenol (100 nmol) did not change plasma AVP, although it decreased arterial pressure and increased heart rate. The increase in plasma AVP by dopamine was not blocked by the preinfusion of the D2-antagonist sulpiride (13 nmol) into the AV3V 10 min before, but was abolished by that of the D1-antagonist SCH-23390 (8 nmol). The effects of phenylephrine on both plasma AVP and the blood pressure were prevented by the preadministration of the alpha-antagonist phenoxybenzamine (13 nmol). However, the pretreatments with phenoxybenzamine, sulpiride or SCH 23390 did not inhibit the responses of AVP, arterial pressure and heart rate caused by PGE2. These antagonists were without significant effect on AVP and other variables when given alone. The infusion sites of PGE2 and the other drugs identified histologically included the AV3V structures such as the organum vasculosum laminae terminalis or its vicinity, median preoptic nucleus, medial preoptic nucleus and periventricular hypothalamic nucleus. Dopamine or phenylephrine administered into the cerebral ventricle at the same dose as used in the AV3V application did not exert a significant effect on plasma AVP, arterial pressure and heart rate. These results suggest that catecholamine receptors in the AV3V may not be involved in the AVP-secreting, tachycardiac and pressor responses evoked by topical action of PGE2 on this area, despite their ability to influence hormone release and cardiovascular function.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1999

Pharmacokinetics and pharmacodynamics of a novel protein kinase inhibitor, UCN-01.

PURPOSE: 7-Hydroxystaurosporine (UCN-01) is a potent protein kinase inhibitor and is being developed as a novel anticancer agent. We describe here its pharmacokinetics and pharmacodynamics in experimental animals. METHODS: The pharmacokinetics of UCN-01 were studied following intravenous (i.v.) administration to mice, rats and dogs at doses of 1-9, 0.35-3.5 and 0.5 mg/kg, respectively. We also studied the pharmacodynamics of UCN-01 (9 mg/kg per day) during and after five consecutive i.v. administrations to nude mice bearing xenografted human pancreatic tumor cells (PSN-1). The concentrations of UCN-01 in plasma and tumor were measured by HPLC using a fluorescence detector. RESULTS: UCN-01 in plasma after i.v. administration was eliminated biphasically in mice and rats, and triphasically in dogs. The elimination half-lives in mice, rats and dogs were 3.00-3.98, 4.02-4.46 and 11.6 h, respectively. The total clearance (Cl(total)) values in mice, rats and dogs were high (1.93-2.64, 2.82-3.86 and 0.616 l/h per kg, respectively). The hepatic clearance (Cl(hepatic)) in rats represented 54.0-81.3% of Cl(total). The volumes of distribution at steady-state in mice, rats and dogs were large (7.89-8.42, 13.0-16.9 and 6.09 l/kg, respectively). These pharmacokinetic parameters were dose-independent in mice and rats. UCN-01 produced significant inhibition of tumor growth during five consecutive i.v. administrations in mice bearing the xenografted PSN-1 cells, and the inhibitory effect continued for 3 days after the final administration. UCN-01 concentrations in tumor tissue were much higher than those in the plasma, and the ratio of tumor to plasma concentrations was about 500 at 24 h after five consecutive doses. CONCLUSIONS: The pharmacokinetic studies showed that UCN-01 has a high clearance and large distribution volume in various experimental animals, and its disposition is linear over the range of doses tested. The pharmacodynamic study showed that UCN-01 is distributed at much higher concentrations in tumor than those in plasma and that it significantly inhibits tumor growth. The high distribution of UCN-01 into tumor cells may contribute to the potent inhibition of tumor growth in vivo.

Alkaloids↗
PubMed1999

Exposure-response relationships in rhinitis and conjunctivitis caused by methyltetrahydrophthalic anhydride.

OBJECTIVE: To examine exposure-response relationships in the occurrence of symptoms of the eyes and airways in workers exposed to methyltetrahydrophthalic anhydride (MTHPA). METHODS: A population of 111 workers from 2 condenser plants (A and B) using epoxy resin with MTHPA underwent a questionnaire survey and serology investigations, and data obtained on 95 subjects in assembly and inspection lines were analyzed for this study. RESULTS: In all, 24 (65%) of 37 workers in plant A and 38 (66%) of 58 workers in plant B had positive MTHPA-specific IgE. The air levels of MTHPA detected in assembly and inspection lines were higher in plant A than in plant B (geometric mean 25.5-63.9 and 4.93-5.49 microg/m3, respectively). IgE-sensitized workers in each plant had significantly (P < 0.05) more complaints regarding the eyes and nose than did unsensitized workers, suggesting that there is an IgE-mediated mechanism in most of these symptoms. The sensitized workers in plant A had higher frequencies for symptoms of the eyes, nose, and pharynx than did those in plant B (P < 0.02). Furthermore, only 15% of persons often displayed work-related symptoms among the 20 symptomatic workers in plant B as compared with 73% of the 26 symptomatic workers in plant A (P < 0.0001). These results can be explained by the difference in the MTHPA levels measured in the lines between the two plants. In plant B the minimal level of MTHPA that was associated with work-related symptoms was 15-22 microg/m3, which was lower than the geometric mean levels detected in assembly and inspection lines in plant A. CONCLUSIONS: These results suggest that MTHPA exposure at levels above 15 microg/m3 should be avoided to prevent the development of occupational allergic diseases in most workers.

Adult↗
PubMed1999

Ductal branch-oriented minimal pancreatectomy: two cases of successful treatment.

Two patients with intraductal papillary-mucinous adenoma of the pancreas were successfully treated by ductal branch-oriented minimal pancreatectomy. We propose this novel less invasive ductal branch-oriented pancreatectomy, as indicated for benign ductal ectasia of the pancreas. The cystically dilated branch duct is identified by intraoperative ultrasonography, intraoperative balloon pancreatography, and injection of indigocarmine into the cyst. The cystically dilated branch is resected from the surrounding pancreas together with minimal removal of the pancreatic parenchyma. The communicating duct and cutting margins are tightly ligated to prevent pancreatic juice leakage and fistula. A drainage tube is placed in the main pancreatic duct whenever possible. Histopathologic examination of the transected branch duct is necessary to check for mucosal extension of dysplastic epithelium. This ductal branch-oriented minimal pancreatectomy is the least invasive pancreatectomy and a suitable operation for branch-type ductal ectasia of the pancreas, which is usually benign.

Aged↗
PubMed1999

The role of percutaneous transhepatic abscess drainage for liver abscess.

To evaluate the efficacy of percutaneous transhepatic abscess drainage (PTAD) as an initial choice of treatment for liver abscess, the medical records of 28 patients with liver abscess were retrospectively analyzed. The patients were predominantly men (23 of 28) with a mean age of 59 years (range, 19-86 years). Their chief complaints were fever (86%), right hypochondralgia (32%), and jaundice (11%). Fifteen of the 28 patients (54%) had hepatobiliary and pancreatic carcinoma, and 31% had postoperative liver abscess. PTAD was performed in 23 patients and surgical drainage in 5. The overall success rate for PTAD was 83%. The success rate for PTAD for patients with multiple abscesses was 83% (5 of 6), compared with a success rate of 82% (14 of 17) for patients with solitary abscess. The prognostic factors for survival were cancer and sepsis and the mortality rate for patients with cancer was 40% (6 of 15) while the mortality rate for patients with sepsis was 56% (5 of 9). As a complication of drainage, 1 patient (4%) in the PTAD group had pleural abscess due to the transpleural puncture. Our findings support the use of PTAD as the primary treatment for liver abscess, as it is safe and effective irrespective of the number of abscesses and the patient's condition.

Adult↗
PubMed1999

Early and late complications of pylorus-preserving pancreatoduodenectomy in Japan 1998.

Early (within 1 month after operation) and late (more than 1 month after surgery) complications after pylorus-preserving pancreatoduodenectomy (PpPD) were analyzed in 1066 Japanese patients collected from 74 authentic institutions in Japan. As early postoperative complications after PpPD, delayed gastric emptying was evident in 46% of patients, pancreatoenterostomy leakage in 16%, intra-abdominal infection in 14%, cholangitis in 8.9%, hepaticojejunostomy leakage in 4.7%, intra-abdominal hemorrhage in 3. 5%, upper gastrointestinal hemorrhage in 3.2%, and duodenojejunostomy leakage in 2.0%. Delayed gastric emptying resolved 1-24 months after PpPD (mean, 3.1 months). The direct operative mortality (death within 1 month after the operation) was 2. 4%. Univariate and multivariate analysis of pancreatoenterostomy leakage showed that male sex (P = 0.0151) and soft consistency of the pancreas (P < 0.0001) were independent significant factors. Univariate analysis of delayed gastric emptying showed that establishment of gastrostomy (P < 0.0001), length of the preserved duodenum (P = 0.0406), gastric juice output (P = 0.0001), length of gastric tube placement (P < 0.0001), and administration of cisapride (P = 0.0059) were significant variants. As late complications, stomal ulcer was evident in 3.6% of patients, cholangitis in 6.7%, and liver abscess in 1.2%. Glucose intolerance appeared in 61 patients, resolved in 15, showed no change in 170, was absent in 695, and was ameliorated in 17. As a result, the dosage of hypoglycemic agents or insulin showed no change in 187 patients, decreased in 16, and increased in 52. Diabetes appeared 0-42 months after PpPD (mean, 102 months). When present, diabetes deteriorated 0-36 months postoperatively (mean, 6.3 months). Univariate analysis of the appearance or deterioration of diabetes showed that diabetes occurred more frequently in the following patients; those with Billroth I reconstruction compared with those with Billroth II (P = 0.0041), those with pancreatogastrostomy vs those with pancreatojejunostomy (P = 0.0229), those with pancreatogastrostomy vs those with end-to-side pancreatojejunostomy (P = 0.0165), and those with total tube drainage vs those with pancreatico-whole thickness anastomosis (P = 0.0392); a high American Society of Anesthesiologist (ASA) score (P = 0.0211) and pancreatoenterostomy leakage (P = 0.0361) were also significant factors. Postoperative body weight loss (>3 kg) was evident in 62% of patients. Body weight loss reached a maximum 4.2 +/- 5.8 months after PpPD (mean, 6.0 kg) and returned to the preoperative level 4.8 months thereafter. These results suggest that PpPD has been performed safely in Japan, the operative mortality being 2.4%. However, delayed gastric emptying was evident in 46% of the patients and pancreatoenterostomy leakage in 16%. Impairment of glucose tolerance occurred in about 10% of patients more than 1 month after PpPD. Therefore, during the early postoperative period, patients should be closely monitored for pancreatoenterostomy leakage and delayed gastric emptying and in the late postoperative period, glucose tolerance should be carefully followed-up.

Adolescent↗
PubMed1999

Malignant rhabdoid tumor of the colon: report of a case.

A malignant rhabdoid tumor of the colon is very rare and only three cases have been previously described. A 76-year-old man was admitted to the hospital complaining of epigastralgia. An elastic mass was palpable in the right upper abdomen. A barium enema and endoscopic examination showed a giant gyrate tumor arising from the cecum. Abdominal ultrasonography and a computed tomography scan revealed the tumor to be located in the colon associated with multiple liver metastases and gallbladder stones. A right colectomy and cholecystectomy were thus performed. The tumor was histologically composed of sheets of large round and polygonal nuclei with vesicular chromatin, and abundant acidophilic cytoplasm, often containing hyalin-like inclusion. The cytoplasm was positive for vimentin and neuron-specific enolase, and hyaline globules of the rhabdoid tumor cells stained positive for cytokeratin in some cells. Transmission electron microscopy showed characteristic rhabdoid cells with an aggregation of intermediate filaments. A histologic diagnosis of malignant rhabdoid tumor of the colon was made. The tumor demonstrated several unusual findings for malignant rhabdoid tumors including diploidy by a flow cytometric analysis, and positive nuclear immunohistochemical staining for p53 protein and Ki-67 antigen. We report herein the third known case of a pure colonic rhabdoid tumor.

Aged↗
PubMed1999

Characterization of metal-substituted Klebsiella aerogenes urease.

Urease possesses a dinuclear Ni active site with the protein providing a bridging carbamylated lysine residue as well as an aspartyl and four histidyl ligands. The apoprotein can be activated in vitro by incubation with bicarbonate/CO2 and Ni(II); however, only approximately 15% forms active enzyme (Ni-CO2-ureaseA), with the remainder forming inactive carbamylated Ni-containing protein (Ni-CO2-ureaseB). In the absence of CO2, apoprotein plus Ni(II) forms a distinct inactive Ni-containing species (Ni-urease). The studies described here were carried out to better define the metal-binding sites for the inactive Ni-urease and Ni-CO2-ureaseB species, and to examine the properties of various forms of Co-, Mn-, and Cu-substituted ureases. Xray absorption spectroscopy (XAS) indicated that the two Ni atoms present in the Ni-urease metallocenter are coordinated by an average of two histidines and 3-4 N/O ligands, consistent with binding to the usual enzyme ligands with the lysine carbamate replaced by solvent. Neither XAS nor electronic spectroscopy provided evidence for thiolate ligation in the inactive Ni-containing species. By contrast, comparative studies of Co-CO2-urease and its C319A variant by electronic spectroscopy were consistent with a portion of the two Co being coordinated by Cys319. Whereas the inactive Co-CO2-urease possesses a single histidyl ligand per metal, the species formed using C319A apoprotein more nearly resembles the native metallocenter and exhibits low levels of activity. Activity is also associated with one of two species of Mn-CO2-urease. A crystal structure of the inactive Mn-CO2-urease species shows a metallocenter very similar in structure to that of native urease, but with a disordering of the Asp360 ligand and movement in the Mn-coordinated solvent molecules. Cu(II) was bound to many sites on the protein in addition to the usual metallocenter, but most of the adventitious metal was removed by treatment with EDTA. Cu-treated urease was irreversibly inactivated, even in the C319A variant, and was not further characterized. Metal speciation between Ni, Co, and Mn most affected the higher of two pKa values for urease activity, consistent with this pKa being associated with the metal-bound hydrolytic water molecule. Our results highlight the importance of precisely positioned protein ligands and solvent structure for urease activity.

Amino Acid Substitution↗
PubMed1999

Shoulder sonography. State of the art.

Since the mid 1980s, sonography has been used to evaluate the rotator cuff. It is inexpensive, well tolerated, rapidly performed, and accurate. With the recent improvements in imaging equipment and refinements in scanning technique, an increasing number of radiologists are performing shoulder sonography. This article emphasizes the pertinent musculoskeletal anatomy, sonographic technique, normal sonographic anatomy, pathophysiology of rotator cuff and biceps tendon disease, sonographic findings of rotator cuff tears, and biceps tendon pathology. The accuracy of ultrasound in diagnosing rotator cuff tears and miscellaneous abnormalities that can be detected with ultrasound also are discussed.

Humans↗
PubMed1999

Post-traumatic brain stem distortion: a case report.

BACKGROUND: Primary traumatic brain stem injury (BSI) lesions are found most frequently in the dorsal or dorsolateral midbrain, whereas distortion of the brain stem itself is exceedingly rare. CASE REPORT: We present a 20-year-old woman with a rare brain stem injury caused by a violent motor vehicle collision. Magnetic resonance imaging at 2 months after injury revealed marked brain stem distortion with loss of the normal shape at the midbrain and pons, which were displaced anteriorly in association with the fracture of the clivus. Moreover, the medulla oblongata showed a loose winding configuration. At discharge about 5 months after injury, the Glasgow Outcome Scale was severe disability. CONCLUSION: This BSI was caused by reciprocal actions of fracture of the clivus and the direct effect on the brain stem caused by acceleration or rotational forces.

Accidents, Traffic↗
PubMed1999

Infection of the erythroid cell line, KU812Ep6 with human parvovirus B19 and its application to titration of B19 infectivity.

A human parvovirus B19 (B19) infectivity assay was developed using the erythroid cell line, KU812Ep6. KU812Ep6 was cloned for high efficiency infection with B19 in vitro, in the presence of erythropoietin by a limiting dilution method from the parent cell line, KU812. B19 was effectively propagated in KU812Ep6 and was detected for B19 antigens, VP1 and VP2. The titers of B19 positive sera measured with KU812Ep6 cells were in the range of 10(6) to 10(8) TCID50 ml. This KU812Ep6 infectivity assay had a 10(3)-10(4.5) higher sensitivity than the colony forming unit-erythroid (CFU-e) injury assay. It was calculated that one TCID50 needed 10(3) B19 genome copies, judging from the infectivity assay and semi-quantitative PCR. The KU812Ep6 infectivity assay was also used to determine infectivity of B19 in vitro, and to evaluate inactivation, as well as clearance of the virus. The inactivation of B19 by heating was carried out and infectivity declined from 10(4) TCID50 ml to < 10 TCID50 ml (lower limit of detection) at 60 degrees C for 3 h or at 70 degrees C for 30 min, but only decreased to 10(2.5) TCID50 ml at 50 degrees C for 8 h.

Antigens, Surface↗
PubMed1999

The effects of prenatal stress on the development of hypothalamic paraventricular neurons in fetal rats.

The present experiments focused on the influence of prenatal stress on the development of neurons of the hypothalamic paraventricular nucleus in the fetal rat, including corticotropin-releasing factor-containing neurons. Prenatal stress was administered by restraining pregnant rats in a small cage for either 30 (30-min stress group) or 240 min (240-min stress group) daily for three days from embryonic day 15 to 17, and the fetal brains were taken on embryonic day 18 for later analysis. Golgi-impregnated neurons of the paraventricular nucleus in the 240-min stress group revealed that the total length of the processes was significantly shorter than in the control (unstressed) and 30-min stress groups. In addition, the 240-min stress group showed an increase in the number of apoptotic cells in the fetal paraventricular nucleus. On the other hand, Golgi-impregnated neurons of the paraventricular nucleus in the 30-min stress group had a greater degree of cell differentiation as manifested by an increase in both the number of branch points and the total length of the processes from the cell body. Furthermore, the fetal paraventricular nucleus in the 30-min stress group showed enhanced corticotropin-releasing factor messenger RNA expression, while the varicosities of corticotropin-releasing factor-containing axons at the median eminence revealed more matured morphology such as shorter intervals between the varicosities. These findings suggest the duration-dependent effects of prenatal stress on the development of fetal hypothalamic paraventricular nucleus neurons, including corticotropin-releasing factor-containing neurons: long-lasting stress causes neurotoxic changes of fetal paraventricular nucleus neurons, whereas short-lasting stress facilitates the development of these fetal brain neurons. These morphological changes induced by prenatal stress may contribute to behavioral changes of the offspring after birth.

Animals↗
PubMed1999

Evaluation of the in vitro activity of six broad-spectrum beta-lactam antimicrobial agents tested against over 2,000 clinical isolates from 22 medical centers in Japan. Japan Antimicrobial Resistance Study Group.

Numerous broad-spectrum beta-lactam antimicrobial agents have been introduced into medical practice since 1985. Although several of these compounds have advanced, infectious disease therapy resistances to them has also emerged world-wide. In 1997, a Japanese 22 medical center investigation was initiated to assess the continued utility of these agents (oxacillin or piperacillin, ceftazidime, cefepime, cefpirome, cefoperazone/sulbactam [C/S], imipenem). The participating medical centers represented a wide geographic distribution, and a common protocol and reagents were applied. Three control strains and a set of challenge organisms were provided to participant centers. Etest (AB BIODISK, Solna, Sweden) strips were used in concurrent tests of these organisms and a qualitative determination of participant skills in the identification of resistant and susceptible phenotypes was established. The quantitative controls demonstrated 97.7-99.2% of MIC values within established QC limits, and the qualitative (susceptibility category) controls documented a 97.3% agreement of participant results with that of reference values (1,320 total results). Only 0.2% of values were false-susceptible errors. After the participant quality was assured, a total of 2,015 clinical strains were tested (10 strains from 10 different organism groups including methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci [CoNS], Escherichia coli, Klebsiella spp., Citrobacter freundii, Enterobacter spp., indole-positive Proteae, Serratia spp., Acinetobacter spp., and Pseudomonas aeruginosa). The staphylococci were uniformly susceptible to all drugs tested except ceftazidime (MIC90, 24 micrograms/ml) that had a potency six- to 12-fold less than either cefepime or cefpirome. Only 3.7 and 45.1% of S. aureus and CoNS were susceptible to ceftazidime, respectively. Among E. coli and Klebsiella spp. the rank order of antimicrobial spectrum was imipenem = "fourth-generation" cephalosporins > ceftazidime > C/S > piperacillin. Possible extended spectrum beta-lactamase phenotypes were identified in 2.9-8.6% of these isolates. Isolates of C. freundii, Enterobacter spp., Proteae, and Serratia spp. that were resistant to ceftazidime and piperacillin remained susceptible to imipenem (0.0-4.5% resistance) and cefepime (0.0-5.0%). Acinetobacters were inhibited best by C/S (99.5% susceptible) and least susceptible to piperacillin (MIC90, > 256 micrograms/ml; 21.7% susceptible) activity. P. aeruginosa isolates were most susceptible to cefepime (83.6%) and this zwitterionic cephalosporin also had the lowest level of resistance (9.1% of MICs at > or = 32 micrograms/ml). Several multi-resistant organisms were identified in participant medical centers including S. marcescens strains resistant to cefepime, imipenem, or both observed in six hospitals. Clonal spread was documented in two medical centers; one hospital having two distinct epidemic clusters. Also a multi-resistant E. cloacae was found in two patients in the same hospital. Evaluations of carbapenem resistance in four species discovered only two strains (in same hospital) among 40 P. aeruginosa isolates (5.0%) with a metallo-enzyme, with nearly all of the remaining strains inhibited by an Ambler Class C enzyme inhibitor (BRL42715) indicating a hyperproduction of a chromosomal cephalosporinase. These results indicate that most newer beta-lactams remain widely useable in medical centers in Japan, but emerging often clonal, resistances have occurred. The overall rank order of antimicrobial spectrum against all ten tested bacterial groups favors the "fourth-generation" cephalosporin, cefepime (96.4% susceptible) as an equal to imipenem (95.9%) > C/S (90.9%) = cefpirome (90.0%) > ceftazidime (75.1%) = penicillins, either oxacillin or piperacillin (76.4%).

Anti-Bacterial Agents↗
PubMed1999

In vitro evaluation of cefepime and other broad-spectrum beta-lactams in 22 medical centers in Japan: a phase II trial comparing two annual organism samples. The Japan Antimicrobial Resistance Study Group.

An antimicrobial resistance surveillance study in Japan is presented representing the second year (Phase II) results from 22 medical centers. Each participant laboratory tested (Etest, AB BIODISK, Solna, Sweden) 100 organisms, 10 strains each from 10 species groups including Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., indole-positive Proteae, Serratia spp., Acinetobacter spp., Pseudomonas aeruginosa, and oxacillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci. Generally only modest variations in the activity of the studied broad-spectrum beta-lactams was observed compared to the study a year before. Specifically, extended spectrum beta-lactamase (ESBL) rates in E. coli increased (2.9 to 8.1%), but the ESBL rate in Klebsiella spp. fell (8.6 to 5.0%). Overall the resistance to the beta-lactams varied from a 4.7% decrease (ceftazidime as a consequence of a modified staphylococcal breakpoint criteria) to a 1.0% increase (cefepime, not significant). The rank order of spectrums in 1998 only changed for cefoperazone-sulbactam (6.1% resistance) that was active against more strains than cefpirome (6.8% resistance). The overall spectrum rank order for the 1998 Japan sample (% resistance) was: cefepime (3.2%) > imipenem (4.1%) > cefoperazone-sulbactam (6.1%) > cefpirome (6.8%) > ceftazidime (8.4%) > piperacillin (19.9%). As with a similar study in 1997, imipenem-resistant isolates of P. aeruginosa and Serratia spp. were discovered with metalloenzymes, usually found in the same medical centers. These results demonstrate the continued in vitro activity and potential sustained clinical efficacy of several broad-spectrum beta-lactams in Japan. Rapid emergence of new or novel resistance were not wide spread using a precise quantitative MIC system. Continued surveillance in this nation would be prudent to document the activity of this clinically valuable class of safe, antimicrobial agents.

Anti-Bacterial Agents↗
PubMed1999

Comparison of treatments for hepatolithiasis: hepatic resection versus cholangioscopic lithotomy.

BACKGROUND: Hepatic resection and percutaneous transhepatic cholangioscopic lithotomy (PTCSL) are the two main approaches to the treatment of hepatolithiasis, but comparisons of longterm followup results have not been adequately reported. STUDY DESIGN: Of 86 patients with hepatolithiasis admitted to our institution between 1980 and 1996, we reviewed 54 patients: 26 who underwent hepatic resection and 28 who underwent PTCSL. Five patients who underwent postoperative cholangioscopic lithotomy were included in the former group. The remainder of the hepatolithiasis patients were not treated by hepatic resection or PTCSL and, therefore, were excluded from this study. Hepatic resections were mainly indicated for left-sided localized intrahepatic calculi, atrophic liver, and possible presence of cholangiocellular carcinoma. PTCSL was performed for right-sided, bilateral or recurrent stones at an average of 6 treatments (range 1 to 20 treatments) for each patient. There were no differences between the two groups in terms of gender or age. The recurrence rate of stones and longterm prognosis were analyzed using the Kaplan-Meier method, and other clinical factors listed below were statistically compared. RESULTS: The rate of complete removal of stones was similarly high in each group (96.2% in the hepatic resection group versus 96.4% in the PTCSL group). The complication (38.5% versus 21.4%) and 5-year survival (85.6% versus 100%) rates were comparable. Remaining bile duct stricture (18.2% versus 60.9%, p < 0.01) and 5-year recurrence rates (5.6% versus 31.5%, p < 0.05) were statistically lower in the hepatic resection group than in the PTCSL group. CONCLUSIONS: Hepatic resection, when combined with postoperative cholangioscopic lithotomy, is a preferable treatment for left-sided stones with strictures and bilateral stones.

Adult↗
PubMed1999

Embryonic lethality, liver degeneration, and impaired NF-kappa B activation in IKK-beta-deficient mice.

IkappaB kinase-alpha and -beta (IKK-alpha and IKK-beta), the catalytic subunits of the IKK complex, phosphorylate IkappaB proteins on specific serine residues, thus targeting IkappaB for degradation and activating the transcription factor NF-kappaB. To elucidate the in vivo function of IKK-beta, we generated IKK-beta-deficient mice. The homozygous mouse embryo dies at approximately 14.5 days of gestation due to liver degeneration and apoptosis. IKK-beta-deficient embryonic fibroblasts have both reduced basal NF-kappaB activity and impaired cytokine-induced NF-kappaB activation. Similarly, basal and cytokine-inducible kinase activities of the IKK complex are greatly reduced in IKK-beta-deficient cells. These results indicate that IKK-beta is crucial for liver development and regulation of NF-kappaB activity and that IKK-alpha can only partially compensate for the loss of IKK-beta.

Animals↗