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Pressure effects on the composition and thermal behavior of lipids from the deep-sea thermophile Methanococcus jannaschii.

The deep-sea archaeon Methanococcus jannaschii was grown at 86 degrees C and under 8, 250, and 500 atm (1 atm = 101.29 kPa) of hyperbaric pressure in a high-pressure, high-temperature bioreactor. The core lipid composition of cultures grown at 250 or 500 atm, as analyzed by supercritical fluid chromatography, exhibited an increased proportion of macrocyclic archaeol and corresponding reductions in aracheol and caldarchaeol compared with the 8-atm cultures. Thermal analysis of a model core-lipid system (23% archaeol, 37% macrocyclic archaeol, and 40% caldarchaeol) using differential scanning calorimetry revealed no well-defined phase transition in the temperature range of 20 to 120 degrees C. Complementary studies of spin-labeled samples under 10 and 500 atm in a special high-pressure, high-temperature electron paramagnetic resonance spectroscopy cell supported the differential scanning calorimetry phase transition data and established that pressure has a lipid-ordering effect over the full range of M. jannaschii's growth temperatures. Specifically, pressure shifted the temperature dependence of lipid fluidity by ca. 10 degrees C/500 atm.

1,2-Dipalmitoylphosphatidylcholine↗

FILAMENT FORMATION BY ESCHERICHIA COLI AT INCREASED HYDROSTATIC PRESSURES.

ZoBell, Claude E. (University of California, La Jolla), and Andre B. Cobet. Filament formation by Escherichia coli at increased hydrostatic pressures. J. Bacteriol. 87:710-719. 1964.-The reproduction as well as the growth of Escherichia coli is retarded by hydrostatic pressures ranging from 200 to 500 atm. Reproduction was indicated by an increase in the number of cells determined by plating on EMB Agar as well as by direct microscopic counts. Growth, which is not necessarily synonymous with reproduction, was indicated by increase in dry weight and protein content of the bacterial biomass. At increased pressures, cells of three different strains of E. coli tended to form long filaments. Whereas most normal cells of E. coli that developed at 1 atm were only about 2 mu long, the mean length of those that developed at 475 atm was 2.93 mu for strain R(4), 3.99 mu for strain S, and 5.82 mu for strain B cells. Nearly 90% of the bacterial biomass produced at 475 atm by strain B was found in filaments exceeding 5 mu in length; 74.7 and 16.4% of the biomass produced at 475 atm by strains S and R(4), respectively, occurred in such filaments. Strain R(4) formed fewer and shorter (5 to 35 mu) filaments than did the other two strains, whose filaments ranged in length from 5 to >100 mu. The bacterial biomass produced at all pressures had approximately the same content of protein and nucleic acids. But at increased pressures appreciably more ribonucleic acid (RNA) and proportionately less deoxyribonucleic acid (DNA) was found per unit of biomass. Whereas the RNA content per cell increased with cell length, the amount of DNA was nearly the same in long filaments formed at increased pressure as in cells of normal length formed at 1 atm. The inverse relationship between the concentration of DNA and cell length in all three strains of E. coli suggests that the failure of DNA to replicate at increased pressure may be responsible for a repression of cell division and consequent filament formation.

Bacterial Proteins↗

Differentiation-induced radioresistance in muscle cells.

DNA damage induces cell cycle arrest and DNA repair or apoptosis in proliferating cells. Terminally differentiated cells are permanently withdrawn from the cell cycle and partly resistant to apoptosis. To investigate the effects of genotoxic agents in postmitotic cells, we compared DNA damage-activated responses in mouse and human proliferating myoblasts and their differentiated counterparts, the myotubes. DNA double-strand breaks caused by ionizing radiation (IR) induced rapid activating autophosphorylation of ataxia-teleangiectasia-mutated (ATM), phosphorylation of histone H2AX, recruitment of repair-associated proteins MRE11 and Nbs1, and activation of Chk2 in both myoblasts and myotubes. However, IR-activated, ATM-mediated phosphorylation of p53 at serine 15 (human) or 18 (mouse) [Ser15(h)/18(m)], and apoptosis occurred in myoblasts but was impaired in myotubes. This phosphorylation could be enforced in myotubes by the anthracycline derivative doxorubicin, leading to selective activation of proapoptotic genes. Unexpectedly, the abundance of autophosphorylated ATM was indistinguishable after exposure of myotubes to IR (10 Gy) or doxorubicin (1 microM/24 h) despite efficient phosphorylation of p53 Ser15(h)/18(m), and apoptosis occurred only in response to doxorubicin. These results suggest that radioresistance in myotubes might reflect a differentiation-associated, pathway-selective blockade of DNA damage signaling downstream of ATM. This mechanism appears to preserve IR-induced activation of the ATM-H2AX-MRE11/Rad50/Nbs1 lesion processing and repair pathway yet restrain ATM-p53-mediated apoptosis, thereby contributing to life-long maintenance of differentiated muscle tissues.

Animals↗

Streptonigrin toxicity in Escherichia coli: oxygen dependence and the role of the intracellular oxidation--reduction state.

The bacterial physiology of streptonigrin toxicity was further investigated. An optimal oxygen concentration for toxicity was inferred from data showing that streptonigrin at 5 micrograms/mL was rapidly lethal to aerobic cultures of Escherichia coli K12JF361, but was without effect on anaerobic cultures and was bacteriostatic to cultures inhibited in 5 atm of oxygen plus 1 atm of air (5 atm O2 plus air) (1 atm = 101.325 kPa). Escherichia coli were protected from a potentially lethal concentration of streptonigrin during anaerobic incubation, whether previously grown anaerobically, aerobically, or in 5 atm O2 plus air. Superoxide dismutase activity increased with increasing oxygen tension in the medium, but was not significantly changed by a lethal concentration of streptonigrin. Although the superoxide dismutase activity was four times greater in E. coli grown in 5 atm O2 plus air than those grown in air alone, the aerobic survival in 5 micrograms/mL streptonigrin was identical, which suggested that superoxide dismutase was not rate limiting for toxicity. Escherichia coli K12 strains deficient in glutathione (KMBL54-129, AB1157-821, and AB1157-830) were protected from streptonigrin poisoning. Dithiothreotol (5.0 mM), diamide (1 mM), methyl viologen (1 mM), and cyanide (10 mM) protected aerobic E. coli from 5 micrograms/mL streptonigrin. These data are also consistent with a model of in vivo streptonigrin toxicity that requires a favorable intracellular oxidation--reduction state and an optimal concentration of molecular oxygen.

Cells, Cultured↗

Acute transverse myelitis: incidence and etiologic considerations.

There have been few population-based studies of acute transverse myelitis (ATM). Therefore, incidence and population selectivity of this disorder in different regions is not well known. Data on all Jewish patients with ATM throughout Israel were collected for the period 1955 through 1975. Based on 62 patients who satisfied rigid diagnostic criteria, the average annual incidence rate was 1.34 per million population. No significant difference in incidence was noted between European/American-born and Afro/Asian-born populations. There was no significant seasonal or annual fluctuation in frequency. In 37% of the patients, a history of infection prior to ATM was reported, more commonly among younger patients. ATM rarely evolved into multiple sclerosis. More than one-third of the patients with ATM made a good recovery; in another one-third recovery was only fair; 14 patients failed to improve and 3 died. If other population-based studies of ATM were undertaken, comparison with our results might shed further light on the causes of this disorder.

Acute Disease↗

Proposed diagnostic criteria and nosology of acute transverse myelitis.

Acute transverse myelitis (ATM) is a focal inflammatory disorder of the spinal cord, resulting in motor, sensory, and autonomic dysfunction. A set of uniform diagnostic criteria and nosology for ATM is proposed to avoid the confusion that inevitably results when investigators use differing criteria. This will ensure a common language of classification, reduce diagnostic confusion, and lay the groundwork necessary for multicenter clinical trials. In addition, a framework is suggested for evaluation of individuals presenting with signs and symptoms of ATM. Best treatment often depends on a timely and accurate diagnosis. Because acute transverse myelopathies are relatively rare, delayed and incomplete work-ups often occur. Rapid and precise diagnosis will ensure not only that compressive lesions are detected and treated but also that idiopathic ATM is distinguished from ATM secondary to a known underlying disease. Identification of etiologies may suggest medical treatment, whereas no clearly established medical treatment currently exists for idiopathic ATM. Establishment of a diagnostic algorithm will likely lead to improved care, although it is recognized that the entire evaluation may not be performed for each patient.

Acute Disease↗

Influence of balloon pressure inflation in patients undergoing primary coronary stent implantation during acute myocardial infarction. A quantitative coronary angiography analysis.

OBJECTIVE: To verify the influence of moderate- or high-pressure balloon inflation during primary coronary stent implantation for acute myocardial infarction. METHODS: After successful coronary stent implantation, 82 patients were divided into 2 groups according to the last balloon inflation pressure: group 1 (> or = 12 to < 16 atm) and group 2 (> or = 16 to 20 atm), each with 41 cases. All patients underwent late coronary angiography. RESULTS: In group 1, the mean stent deployment pressure was 13.58 +/- 0.92 atm, and in the group 2 it was 18.15 +/- 1.66 atm. Stents implanted with moderate pressures (> or = 12 to < 16 atm) had a significantly smaller post-procedural minimal lumen diameter, compared to with those with higher pressure, with lesser acute gain (2.7 +/- 0.4 mm vs 2.9 +/- 0.4 mm; p = 0.004), but the late lumen loss (0.9 +/- 0.8 mm vs 0.9 +/- 0.6 mm) and the restenosis (22% vs. 17.1%) and target-vessel revascularization rates (9.8% vs 7.3%) were similar between the groups. CONCLUSION: During AMI stenting, the use of high pressures (> or = 16 atm) did not cause a measurable improvement in late outcome, either in the late loss, its index, and the net gain, or in clinical and angiographic restenosis rates.

Adolescent↗

Targeting chk2 kinase: molecular interaction maps and therapeutic rationale.

Most anticancer drugs presently used clinically target genomic DNA. The selectivity of these anticancer drugs for tumor tissues is probably due to tumor-specific defects suppressing cell cycle checkpoints and DNA repair, and enhancing apoptotic response in the tumor. We will review the molecular interactions within the ATM-Chk2 pathway implicating the DNA damage sensor kinases (ATM, ATR and DNA-PK), the adaptor BRCT proteins (Nbs1, Brca1, 53BP1, MDC1) and the effector kinases (Chk2, Chk1, Plk3, JNK, p38). The molecular interaction map convention (MIM) will be used for presenting this molecular network (http://discover.nci.nih.gov/mim/). A characteristic of the ATM-Chk2 pathway is its redundancy. First, ATM and Chk2 phosphorylate common substrates including p53, E2F1, BRCA1, and Chk2 itself, which suggests that Chk2 (also known as CHECK2, Cds1 in fission yeast, and Dmchk2 or Dmnk or Loki in the fruit fly) acts as a relay for ATM and/or as a salvage pathway when ATM is inactivated. Secondly, redundancy is apparent for the substrates, which can be phosphorylated/activated at similar residues by Chk2, Chk1, and the polo kinases (Plk's). Functionally, Chk2 can activate both apoptosis (via p53, E2F1 and PML) and cell cycle checkpoint (via Cdc25A and Cdc25C, p53, and BRCA1). We will review the short list of published Chk2 inhibitors. We will also propose a novel paradigm for screening interfacial inhibitors of Chk2. Chk2 inhibitors might be used to enhance the tumor selectivity of DNA targeted agents in p53-deficient tumors, and for the treatment of tumors whose growth depends on enhanced Chk2 activity.

Animals↗

A new model of concussive brain injury in the cat produced by extradural fluid volume loading: II. Physiological and neuropathological observations.

This study examined physiological and histopathological changes in the cat produced by a new experimental fluid injury device. Spontaneously breathing (N = 14) and artificially ventilated (N = 45) cats were subjected to systemically varied magnitudes of fluid percussion brain injury. Within certain injury ranges, increasing magnitudes of fluid percussion injury produced increasing durations of apnea, as well as greater transient increases in mean arterial blood pressure, intracranial pressure and cerebral perfusion pressure. Acute increases in intracranial pressure may have been related to cerebral vasodilatation produced by the systemic hypertension following brain injury. Injuries associated with pressure transients greater than 10 atm ms produced concussive responses, including irreversible apnea in spontaneously breathing cats and temporary pupillary dilatation, increases in heart rate and mean arterial blood pressure in artificially ventilated cats. Injuries greater than 39 atm ms frequently produced histopathological and physiological indices of significant irreversible brain damage, including fixed and dilated pupils, systemic cardiovascular hypotension and deteriorating blood gases. Injury magnitudes less than 20 atm ms did not produce macroscopic evidence of histopathology, intermediate injury ranges produced increasing evidence of subarachnoid and petechial hemorrhage while injury levels greater than 40 atm ms frequently produced significant histopathology including massive hematomas. Injury greater than 10 atm ms resulted in opening of the blood-brain barrier, as assessed by extravasation of horseradish peroxidase. Injury greater than 19 atm ms produced suppression of EEG amplitudes which did not recover for up to 40 minutes after injury. These data provide detailed information on the physiological and histopathological consequences of fluid percussion injury in the cat and indicate that this modified fluid percussion apparatus can produce graded levels of brain injury similar to those previously reported for fluid percussion injury.

Animals↗

Laparoscopic augmentation cystoplasty with different biodegradable grafts in an animal model.

PURPOSE: Recently a variety of biodegradable organic materials have been used for bladder wall replacement. We sought to study the effectiveness of 4 different types of biodegradable materials for bladder augmentation using laparoscopic techniques. MATERIALS AND METHODS: Thirty one minipigs underwent successful transperitoneal laparoscopic partial cystectomy and subsequent closure (6 control) or patch augmentation (25): porcine bowel acellular tissue matrix (ATM) (6), bovine pericardium (BPC) (6), human placental membranes (HPM) (6) or porcine small intestinal submucosa (SIS) (7). An intracorporeal suturing technique with the EndoStitch device (U.S. Surgical, Norwalk, CT) and Lapra-Ty clips (Ethicon, Enodsurgery Inc. Cincinnati, OH) was used to anastomose the graft to the bladder wall. Postoperatively, a urethral catheter was left for one week. Bladders were evaluated by cystoscopy at 6 and 12 weeks and harvested at 12 weeks. RESULTS: Grafts remained in place in all groups except for the BPC group, where all grafts failed to incorporate. For the ATM and SIS groups, at 6 weeks, there was mucosal coverage of the grafts without evidence of encrustation. In the control group, at 12 weeks, the bladder capacity was 23% less than preoperatively. In the ATM, HPM and SIS groups, at 12 weeks, the bladder capacities were larger than preoperatively by 16%, 51% and 43% respectively; also the grafts had contracted to 70%, 65%, and 60% of their original sizes, respectively. Histologically, there was patchy epithelialization of ATM and SIS grafts with a mixture of squamoid and transitional cell epithelia. The graft persisted as a well-vascularized fibrous band in HPM, ATM, and SIS without evidence of significant inflammatory response. CONCLUSION: A laparoscopic technique for partial bladder wall replacement using a free graft is feasible. The biodegradable grafts of ATM, HPM and SIS are tolerated by host bladder and are associated with predominantly only mucosal regeneration at 12 weeks post-operatively.

Animals↗

Benefits of cutting balloon before stenting.

UNLABELLED: The objectives of this study were to prospectively evaluate the safety and feasibility of pretreating the culprit coronary artery lesion with cutting balloon (CB) angioplasty prior to coronary stent implantation. BACKGROUND: The CB has shown promise for the treatment of de novo coronary lesions and in-stent restenoses, but has not been prospectively evaluated for use prior to stent implantation. METHODS: Patients with significant coronary artery disease requiring stent placement had the culprit lesion pretreated with a CB. Stents were deployed to cover the entire segment pretreated with the CB. Intravascular ultrasound (IVUS) was used to interrogate acute luminal gain following stent implantation and after serial post-deployment inflation pressures ranging from 8 16 atmospheres (atm). Coronary angiograms were also obtained to determine luminal diameter. In-hospital complication rates were noted. RESULTS: Fifty-one patients were treated with the CB prior to stent implantation. Minimal stent cross-sectional area increased significantly with increasing inflation pressures between 8 and 10 atm (p < 0.0004) and between 10 and 12 atm (p = 0.0049). The minimal stent cross-sectional area achieved, as measured by IVUS, was 7.59 mm2 2.00 mm2 at 8 atm, 8.06 mm2 1.53 mm2 at 10 atm and 8.72 mm2 1.58 mm2 at 12 atm. The final in-stent percent diameter stenosis was lower compared to pre-procedure (5.4% 12.2% versus 64.1% 14.1%, respectively) by quantitative coronary angiography. CONCLUSION: The CB can be used prior to stent implantation to attain significant gains in minimal stent cross-sectional areas at relatively low pressures.

Aged↗

Molecular cloning and characterization of the catalytic domain of zebrafish homologue of the ataxia-telangiectasia mutated gene.

Inherited biallelic mutations of the ATM (ataxia-telangiectasia mutated) gene in humans cause ataxia-telangiectasia, a rare autosomal recessive disorder associated with progressive neuro-degeneration, cancer predisposition, immunodeficiency, and hypersensitivity to ionizing radiation. The ATM gene is highly conserved across a wide range of species. In an attempt to establish a zebrafish (Danio rerio) model of ataxia-telangiectasia, we cloned the coding sequence of the catalytic domain of the zebrafish homologue of ATM and found it to contain an open reading frame encoding 907 amino acids at the carboxyl terminus of the zebrafish ATM (zATM). The catalytic domain of zATM shares 67% and 66% homology with human ATM (hATM) and mouse ATM (mATM), respectively. The full-length mRNA encoding zATM is found to be approximately 11 kb by Northern hybridization, and the expression of zATM is observed in different adult and embryonic tissues. Overexpression of a kinase-inactive zATM domain in human cells has a dominant-negative effect against hATM function. Expression of the altered zATM in ZF4 cells leads to an A-T-like phenotype in response to ionizing radiation. These results taken together indicate that zATM is the homologue of hATM. Furthermore, using the kinase-inactive form of zATM should allow manipulation of zATM function in fish cells.

Amino Acid Sequence↗

[Expression and clinical significance of P53 pathway-associated proteins in pancreatic carcinoma].

BACKGROUND & OBJECTIVE: P53 pathway plays a critical role in carcinogenesis of pancreatic carcinoma. However, its trigger and function mechanisms have seldom been reported. This study was to investigate the expression and clinical significance of P53 pathway-related proteins ATM, P53, Mdm2, and P21(WAF/CIP1) in pancreatic carcinoma. METHODS: The expression of ATM, P53, Mdm2, and P21(WAF/CIP1) proteins in 167 specimens of pancreatic carcinoma and 112 specimens of non-cancer pancreatic tissues was detected by tissue microarray and immunohistochemistry. RESULTS: The positive rates of P53 and Mdm2 were higher in pancreatic carcinoma than in non-tumor pancreatic tissues (57.5% vs. 6.3%, 64.1% vs. 5.4%, P < 0.01), while the positive rates of ATM and P21(WAF/CIP1) were lower in pancreatic carcinoma than in non-tumor pancreatic tissues (67.7% vs. 82.1%, 39.5% vs. 71.4%, P < 0.05). ATM expression in pancreatic carcinoma was related to patients' age (P < 0.05). P53 expression was related to tumor differentiation, lymph node metastasis, and nerve involvement (P < 0.05). Mdm2 expression was related to tumor differentiation (P < 0.05). P21(WAF/CIP1) expression was related to patients' age and nerve involvement (P < 0.05). There were statistical correlations between these 4 proteins (P < 0.05). CONCLUSIONS: Overexpression of P53 and Mdm2 and loss of ATM and P21(WAF/CIP1) expression may contribute to the tumorigenesis and development of pancreatic carcinoma. The 4 proteins may affect cell transformation and tumorigenesis through ATM-Mdm2-P53-P21(WAF/CIP1) pathway. Co-detection of P53 and Mdm2 can be used to evaluate the differentiation of pancreatic carcinoma.

Adult↗

A prospective, randomized clinical trial comparing two hyperbaric treatment protocols for carbon monoxide poisoning.

INTRODUCTION: The optimal hyperbaric oxygen (HBO2) treatment protocol for acute carbon monoxide (CO) poisoning is unknown. This is indicated by one study that found 18 different protocols to treat CO poisoning by North American multiplace hyperbaric facilities. A pilot study was conducted to evaluate the feasibility of randomizing patients to different protocols and to determine whether any large differences in clinical outcome were present between the two most common protocols. METHODS: Adult patients with accidental CO poisoning resulting in transient loss of consciousness, presentation to the emergency department within 12 hours, primary language English, high school education, and residence within 100 miles of the hyperbaric facility were recruited. Enrolled patients were randomized to one HBO2 treatment at 2.4 atmospheres absolute (atm abs) pressure with 90 minutes of 100% oxygen breathing vs. treatment by the US Air Force CO protocol (3.0 atm abs maximum pressure). A neurocognitive screening test was performed immediately after hyperbaric treatment and repeated 14-21 days later. RESULTS: From 1995 to 2002, 30 patients age 21 to 88 years were randomized, 18 to treatment at 2.4 atm abs and 12 to 3.0 atm abs. Average carboxyhemoglobin level for the population was 24.8 +/- 8.8% (mean +/- SD). Delay to hyperbaric treatment averaged 313 +/- 129 minutes. Neither variable was different between treatment groups. Six patients had abnormal neurocognitive testing immediately following hyperbaric treatment, 4 in the 2.4 atm abs group (22%) and 2 in the 3.0 atm abs group (17%) (P=0.71). One patient in each group demonstrated abnormality on delayed testing (p=0.75). One in each group did not return for follow-up. CONCLUSIONS: It is feasible to randomize CO-poisoned patients to different hyperbaric treatment protocols. Determination of differences in efficacy between treatment protocols will require a large multicenter trial with the use of detailed neurocognitive testing.

Adult↗

Hyogo ear bank experience with allograft tympanoplasty--review of tympanoplasties on 68 ears.

Allograft tympanoplasties on 68 ears done between October, 1980 and December, 1986 were analyzed from the viewpoint of graft take rate and hearing improvement, and also the results were compared between draining and nondraining ears as well as among three stabilizing methods of the transplanted tympanic membrane (Type I: allograft tympanic membrane (ATM) covered with reflected epithelium; Type II: entirely covered ATM with fascia; and Type III: ATM reinforced with thin crescent fascia) and four groups of allograft materials (Group I: ATM with attached malleus and incus en bloc; Group II: ATM with attached malleus; Group III: ATM attached malleus and incus columella; and Group IV: two stage surgery with Group III material). Among the three types of stabilization in draining ears, the anatomic success rate of the tympanic membrane transplant was 27% in Type I, 56% in Type II and 90% in Type III, while in nondraining ears it was 81%, 88%, and 100%, respectively. The success rate for hearing improvement in draining ears was 40% in Group A, 44% in Group B, 33% in Group C, and in nondraining ears, it was 82%, 100%, and 82%, respectively. Our results show that allograft tympanoplasty can be successful for a well-controlled middle ear with good utility of the areolar fascia in stabilization.

Graft Survival↗

[Activity of 9 beta-lactam antibiotics combined with clavulanic acid or sulbactam against the strains of broad-spectrum beta-lactamase (CTX-1) producing Enterobacteriaceae isolated at the Henri Mondor Hospital].

Minimal inhibitory concentrations (MICs) of seven cephalosporins: cefotaxime (CTX), ceftriaxone (CRO), ceftazidime (CAZ), latamoxef (MOX), cefoxitin (FOX), cefotetan (CTT) and CM 40876 (CM), of aztreonam (ATM) and imipenem (IPM) were evaluated by agar dilution with and without 5 mg/l of clavulanic acid (AC) or sulbactam (SB) for 28 strains isolated in 1986 (15 K. pneumoniae, 3. K. oxytoca, 4 E. coli, 4 E. cloacae, 1 E. aerogenes and 1 C. freundii). Comparatively to MICs of sensitive strains and to those of cured variants, MICs of these strains were very increased for CTX, CRO, ATM (mode MIC: 1 mg/l), and CAZ (2); weakly increased for MOX and CTT (0.25), and identical for IMP (0.12-0.25), CM (0.06) and FOX (2-4), except for Enterobacter and Citrobacter (64). Association with AC or SB did not modify MICs of FOX, CM and IMP. For the other antibiotics, MICs were reduced by addition of AC: Klebsiella: 5 log2 for CTX and CRO, 4 for CAZ and ATM, 2 for MOX and CTT; E. coli: 4 log2 for CTX and ATM, 3 for CRO and CAZ, 1 for MOX and CTT; Enterobacter and Citrobacter 2 log2 for CTX, CRO, CAZ and ATM, 1 for MOX and CTT. With SB, decrease of MICs was two to for fold lesser than with AC. AC, and less efficiently SB, restored activity of CTX, CRO, CAZ and ATM on CTX-1 producing Enterobacteriaceae, particularly Klebsiella and E. coli. It was the same for MOX and CTT, weakly affected by this resistance. AC and SB had not effect on FOX, CM and IPM which remained active on these strains.

Anti-Bacterial Agents↗

Effects of hyperbarism on central respiratory drive and respiratory pattern in humans.

The aim of our study was to evaluate the effects of increasing pressure (from 1 to 3 and 6 atm abs) on respiratory drive, respiratory pattern, and inspiratory impedance of the respiratory system. Seven healthy volunteers were studied during a dry compression to 6 atm abs in a hyperbaric multiplace chamber. We observed a significant increase in tidal volume, P0.1 (the pressure generated in the airway after 100 ms of inspiration against a closed inspiratory line), Ttot, and Ti, and a significant respiratory rate reduction with increasing pressure from 1 to 3 atm.abs; P0.1 also increased significantly when comparing 3 and 6 atm abs measurement with 1 atm abs. The P > 0.01 and P0.1/(VT/Ti) showed a significant progressive increase compared with 1 atm abs. In conclusion, the passage from 1 to 3 and 6 atm abs causes, in healthy subjects at rest, an increase in the central respiratory drive activity, evaluated with P0.1 measurement. The response to the respiration system is an increase in tidal volume and Ti with a decrease in respiratory rate.

Adult↗

The role of ataxia-telangiectasia heterozygotes in familial breast cancer.

The role of ataxia-telangiectasia (AT) heterozygotes in breast cancer has been controversial. We have found previously an overrepresentation (3.4%) of ATM mutations in a subset of 88 selected breast cancer patients with a family history of breast cancer, leukemia, and lymphoma. This prevalence is comparable to the estimated value (3.8%) from epidemiological study. To further examine the possibility that ATM is correlated to breast cancer, we screened for ATM germ-line mutations in another 100 breast cancer patients with a family history of breast cancer. We used the protein truncating test and found one new germ-line mutation. This figure (1%) is consistent with the observed 0.2-1% carrier frequency for AT. We also studied breast tumors from ATM mutants, and three showed retention of both alleles, whereas the fourth showed loss of the mutant allele. We conclude that the contribution of heterozygous ATM mutations to familial breast cancer is minimal. Even if the ATM gene were causative in these cases, it is not likely to act as a tumor suppressor.

Ataxia Telangiectasia↗