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Le microbiote intestinal (ou flore intestinale) est un ensemble de bactéries hébergées par l’être humain et vivant en symbiose avec son hôte. Étroitement associé au tractus intestinal et interagissant avec lui, il ne constitue pas un tissu ni un organe, mais un supra-organisme. La perturbation du dialogue entre les bactéries et les cellules humaines est un facteur de risque, voire la cause de différentes maladies. La restauration de ce dialogue par le transfert de microbiote intestinal, d’un sujet sain à un patient dont l’équilibre de la flore intestinale a été rompu, constitue une nouvelle approche thérapeutique. Si son effet exact échappe encore à la compréhension scientifique, son bénéfice clinique est établi pour une indication, et en cours d’essais pour d’autres. La contribution du microbiote intestinal à l’équilibre physiologique humain appelle ainsi des recherches internationales quant à l’état des connaissances et des techniques, ainsi qu’au cadre juridique et éthique des pratiques. Cet article fait le point sur les questions posées par cet acte thérapeutique

ABSTRACTAlthough antiretroviral treatment availability has improved, the virological monitoring of patients remains largely uneven across regions. In addition, viral quantification tests are suffering from human immunodeficiency virus type 1 (HIV-1) genetic diversity, fueled by the emergence of new recombinants and of lentiviruses from nonhuman primates. We developed a real-time reverse transcription-PCR (RT-PCR) assay that is relatively inexpensive and able to detect and quantify all circulating forms of HIV-1 and its simian immunodeficiency virus (SIV) precursors, SIVcpz and SIVgor. Primers and a probe were designed to detect all variants of the HIV-1/SIVcpz/SIVgor lineage. HIV-1 M plasma (n= 190; 1.68 to 7.78 log10copies/ml) representing eight subtypes, nine circulating recombinant forms, and 21 unique recombinant forms were tested. The mean PCR efficiency was 99%, with low coefficients of intra- and interassay variation (<5%) and a limit of quantification of <2.50 log10copies/ml, with a 200-µl plasma volume. On the studied range, the specificity and the analytical sensitivity were 100 and 97.4%, respectively. The viral loads were highly correlated (r= 0.95, P< 0.0001) with the reference method (generic HIV assay; Biocentric) and had no systematic difference, irrespective of genotype. Furthermore, 22 HIV-1 O plasmas were screened and were better quantified compared to the gold-standard RealTime HIV-1 assay (Abbott), including four samples that were only quantified by our assay. Finally, we could quantify SIVcpzPtt and SIVcpzPts from chimpanzee plasma (n= 5) and amplify SIVcpz and SIVgor from feces. Thus, the newly developed real-time RT-PCR assay detects and quantifies strains from the HIV-1/SIVcpz/SIVgor lineage, including a wide diversity of group M strains and HIV-1 O. It can therefore be useful in geographical areas of high HIV diversity and at risk for the emergence of new HIV variants.

This paper reports methods developed to maximize the overall reflectance second-surface silvered glass. The reflectance at shorter wavelengths is increased with the aid of a dielectric enhancing layer between the silver and the glass, while at longer wavelengths it is enhanced by use of glass with negligible iron content. The calculated enhancement of reflectance, compared to unenhanced silver on standard low-iron float glass, corresponds to a 4.4% increase in reflectance averaged across the full solar spectrum, appropriate for CSP, and 2.7% for CPV systems using triple junction cells. An experimental reflector incorporating these improvements, of drawn crown glass and a silvered second-surface with dielectric boost, was measured at NREL to have 95.4% solar weighted reflectance. For comparison, non-enhanced, wetsilvered reflectors of the same 4 mm thickness show reflectance ranging from 91.6 - 94.6%, depending on iron content. A potential drawback of using iron-free drawn glass is reduced concentration in high concentration systems because of the inherent surface errors. This effect is largely mitigated for glass shaped by slumping into a concave mold, rather than by bending.

The gut microbiota is a very complex ecosystem which interacts extensively with the host, influencing multiple metabolic and physiological functions. Several diseases have been shown to be associated with specific alterations in gut microbiota. It is more and more underscored as playing a major role in the development of insulin resistance and inflammation associated with excess weight gain.

The aim of this review was to examine the characteristics of the faecal calprotectin assay in neonates and the evidence for its use as a noninvasive marker of intestinal illnesses during the neonatal period. Bibliographic searches were performed in the MEDLINE electronic database up to February 2010 looking for the following words (all fields): “infants” or “neonates” and “calprotectin.” Twenty studies, in which 1180 neonates were enrolled, were selected. During the neonatal period, calprotectin levels are characterized by significantly higher values in both healthy full-term and preterm infants during their first year of life compared with reference values established for children and adults. No difference was observed according to gestational age or birth weight, whereas a higher faecal calprotectin level was detected during intestinal distress in neonates with either inflammatory or patent digestive alterations. Despite high interindividual variations, cutoff levels are proposed to identify infants with a high risk of intestinal illnesses. Compared with adults and children, healthy full-term and preterm neonates have high calprotectin levels. The measurement of calprotectin levels in faeces can be a promising noninvasive clinical screening test for intestinal distress in neonates.

ABSTRACTWe recently reported the frequent detection of polyomaviruses (BK virus [BKV] or simian virus 40 [SV40]) in 46% of stool samples from hospitalized children. In order to determine if adults exhibit fecal shedding of polyomavirus, single stool specimens from healthy adults were evaluated by PCR. Overall, 20 (18.2%) of 110 specimens were positive for human polyomaviruses: 9 with BKV, 9 with JC virus (JCV), 1 with SV40, and 1 with both JCV and SV40. Among the 94 subjects without immune compromise, 17 (18.1%) were excreting polyomaviruses. This shedding frequency in adults was significantly lower than that observed in children (P< 0.001). These findings support the hypothesis that the gastrointestinal tract may be a site of polyomavirus persistence, and they suggest a fecal-oral route of viral transmission.

Polyomavirus infection causes nephropathy after kidney transplantation but has not been thoroughly investigated in nonrenal organ transplantation.

This study aimed to determine cutoff levels for fecal calprotectin as a marker of intestinal distress in preterm neonates. A total of 126 infants born at a median gestational age of 33 weeks (range 25.7–35 weeks) were enrolled. Samples (n = 312) were collected weekly from the end of the first week of life until the end of the first month and if any gastrointestinal event occurred. Receiver operating characteristic curves analysis gave cutoff values of 363 µg/g (sensitivity 0.65, specificity 0.82) and 636 µg/g (sensitivity 0.72, specificity 0.95) for the development of mild or severe enteropathy.

Premature birth results in a delayed and abnormal qualitative pattern of gut colonization. This abnormal pattern is thought to affect intestinal development and contribute to a higher risk of gastrointestinal infectious diseases such as neonatal necrotizing enterocolitis (NEC). In particular, bifidobacteria are thought to play a major role. We therefore studied bifidobacterial colonization in preterm infants during the first month of life.

We analysed whether mutations associated with resistance to antiretroviral (ARV) drugs circulate among treatment-naive HIV-1-infected individuals at a period when these drugs started to become more widely available in Africa. Overall, major resistance mutations in the polgene, as defined by the International AIDS Society Resistance Testing-USA panel, were observed in 16 treatment-naive individuals. Eight of the 97 patients tested in Burkina Faso bore mutations conferring resistance to one drug class of ARV drugs: two to nucleoside reverse transcriptase inhibitors (NRTIs; M41L [n=1], M41L+T69S [n=1]), four to non-NRTIs (NNRTIs; V106A/V [n=1] and V108I [n=3]) and two to protease inhibitors (PIs; L33F [n=2]). In Cameroon, resistance mutations were identified in 8 of 102 patients: three to PIs (M46I/L [n=2], L33F [n=1]), three to NRTIs (T69N/T [n=1], M184V [n=1], A62V [n=1]) and two to NNRTIs (P236L [n=1], V108I [n=1]). It is important to note that not all geno-typic drug-resistance algorithms give similar interpretations to the observed mutations. Population surveillance for ARV drug resistance is required and should be included in all implementation programmes.

Despite extensive research, the pathogenesis of neonatal necrotizing enterocolitis (NEC) remains elusive. The aim of our work was to investigate the role of bacterial strains involved in NEC in gnotobiotic quails as experimental model. Six groups of germ-free quails that were fed a lactose diet were associated with Klebsiella pneumoniae, Clostridium perfringens, C. difficile, C. paraputrificum, or C. butyricum(two strains). Implantation level, incidence of cecal lesions, production of short-chain fatty acids, and histologic lesions of the cecal wall were investigated. Whatever the strain, the implantation level was high (109UFC/g). Neither K. pneumoniaenor C. difficileinduced any cecal lesions. In contrast, the four other clostridial strains led to cecal NEC-like lesions with a variable occurrence: four of 12 quails for C. perfringens, eight of 12 quails for C. paraputrificum, and the same highest value, nine of 12 quails and eight of 10 quails for both C. butyricumstrains. Gross aspects of the lesions may be linked to the short-chain fatty acid profiles and/or concentrations: thickening of the cecal wall (C. butyricumand C. perfringens) with high proportion of butyric acid, hemorrhages (C. paraputrificum) with high proportion of iso-butyric acid, and presence of other iso-acids. In addition, C. butyricumwas characterized by pneumatosis, linked to a high gas production. Microscopic aspects confirmed the presence of edemas and intramucosa hemorrhages. Clostridia species, whose role is controversial, seem to be strongly implicated in NEC through excessive production of butyric acid as a result of colonic lactose fermentation. These results call for anaerobe detection in feces of infants who have NEC.

Seroprevalence studies indicate that most primary infections with BK virus (BKV) and JC virus (JCV) occur in the first and second decades of life, respectively. Relatively little is known about the transmission of these agents, including the primary source of human exposure, the portal of entry, and the pathophysiology of life‐long viral persistence. We sought to determine if simian virus 40 (SV40) excretion could be detected in the urine of healthy children and to define the age‐related prevalence of polyomavirus shedding in this population. A point prevalence study of polyomavirus shedding was conducted in healthy children using rigorous enrollment criteria. Urine samples were collected from healthy children, age from 3 to 18 years, during routine evaluation at two urban pediatric clinics. Qualitative PCR analysis was performed using primers that detect a conserved region of the T‐antigen gene of BKV, JCV, and SV40. The identity of polyomaviruses detected was determined by DNA sequence analysis and/or PCR amplification of other regions of the viral genomes. Seven of 72 (9.7%) urine samples were positive for polyomaviruses: three with BKV (ages 4, 6, 13), two with SV40 (ages 6, 16), two with BKV and SV40 co‐excretion (ages 6, 15), and none with JCV. DNA sequence analysis confirmed the identity of viruses detected. These results suggest that the timing of SV40 infections in humans may be similar to that of BKV and that urine from healthy children could contribute to the ubiquity of BKV infection early in life. J. Med. Virol. 75:447–454, 2005. © 2005 Wiley‐Liss, Inc.

Objectives: The aim of our study was to analyse the antibiotic susceptibility of various strains of Bifidobacterium spp. to a wide range of antimicrobial agents. Methods: Fifty strains belonging to eight species of bifidobacteria, isolated from humans, animals or probiotic products, were tested for susceptibility to 30 antibiotics by disc diffusion on Brucella agar supplemented with 5% laked sheep blood and vitamin K1 (1 mg/L). MICs of nine anti-anaerobe agents, including three new molecules (telithromycin, linezolid and gatifloxacin), were determined using the reference agar-dilution method. Results: All strains of bifidobacteria, whatever the species, were sensitive to penicillins: penicillin G, amoxicillin (MIC50 0.06 mg/L), piperacillin, ticarcillin, imipenem and usually anti-Gram-positive antibiotics (macrolides, clindamycin, pristinamycin, vancomycin and teicoplanin). Susceptibility to cefalothin and cefotetan was variable. Most isolates (70%) were resistant to fusidic acid. As expected, high resistance rates were observed for aminoglycosides. Metronidazole, an agent known for its anti-anaerobe activity, was ineffective against 38% of the strains. The newly commercialized molecules, telithromycin, linezolid and gatifloxacin, were active with MIC50S of 1 mg/L. The only variation in susceptibility observed among the different species concerned Bifidobacterium breve, which appeared to be generally more resistant. Potentially acquired resistance was only observed against tetracycline and minocycline, in 14% of the strains. Conclusions: With regard to a general concern about the safety of probiotics, such as potential transferability of resistance determinants, bifidobacteria, with their low natural and acquired resistance to 30 antibiotics, appear risk-free.

ABSTRACTEarly-onset group B streptococcal (GBS) infections remain a leading cause of morbidity and mortality in infants. To prevent the vertical transmission of GBS and neonatal GBS infection, guidelines recommend intrapartum penicillin or amoxicillin prophylaxis. This intrapartum antibiotic prophylaxis (IAP) is suspected to favor colonization by antibiotic-resistant bacteria. However, the effects of this prophylaxis on the patterns of acquisition of gastrointestinal bacterial flora in infants have never been studied. We collected stool samples from 3-day-old infants born to mothers who received intrapartum amoxicillin (antibiotic-exposed group; n= 25) and to untreated mothers (non-antibiotic-exposed group; n= 25). The groups were matched for factors known to affect intestinal microbial colonization: gestational age, type of delivery, and type of feeding. Qualitative and quantitative differential analyses of the bacterial flora in stool samples were performed. Similar numbers of infants in the non-antibiotic-exposed and antibiotic-exposed groups were colonized by aerobic bacteria and amoxicillin-resistant enterobacteria (75 and 77%, respectively) (P= 0.79). In contrast, significantly fewer infants in the antibiotic-exposed group than in the non-antibiotic-exposed group were colonized by anaerobic bacteria, especially Clostridium(12 and 40%, respectively) (P< 0.05). Regarding intestinal bacterial colonization, the differences between antibiotic-exposed and non-antibiotic-exposed infants were remarkably few. The only statistically significant effect was the reduced initial bacterial colonization by Clostridiumin the antibiotic-exposed group. In our study, the use of IAP did not favor colonization by ß-lactam-resistant bacteria. However, further evaluations are required to highlight the potential risks of the widespread use of antibiotics to prevent early-onset GBS infection.

SUMMARYThe polyomavirus simian virus 40 (SV40) is a known oncogenic DNA virus which induces primary brain and bone cancers, malignant mesothelioma, and lymphomas in laboratory animals. Persuasive evidence now indicates that SV40 is causing infections in humans today and represents an emerging pathogen. A meta-analysis of molecular, pathological, and clinical data from 1,793 cancer patients indicates that there is a significant excess risk of SV40 associated with human primary brain cancers, primary bone cancers, malignant mesothelioma, and non-Hodgkin's lymphoma. Experimental data strongly suggest that SV40 may be functionally important in the development of some of those human malignancies. Therefore, the major types of tumors induced by SV40 in laboratory animals are the same as those human malignancies found to contain SV40 markers. The Institute of Medicine recently concluded that “the biological evidence is of moderate strength that SV40 exposure could lead to cancer in humans under natural conditions.” This review analyzes the accumulating data that indicate that SV40 is a pathogen which has a possible etiologic role in human malignancies. Future research directions are considered.

Between 1955 and 1963, millions of individuals worldwide received vaccines contaminated with polyomavirus simian virus (SV)40. Recent data suggest that some individuals may develop renal dysfunction related to SV40 infection, including individuals too young to have received contaminated vaccines.

Studies conducted before the introduction of highly active antiretroviral therapy (HAART) suggested that the risk of Hodgkin lymphoma in persons with human immunodeficiency virus (HIV) infection was increased. However, little is known about the features of this malignancy in patients receiving HAART. From January 1996 through December 2001, 23 cases of Hodgkin lymphoma were diagnosed among 3,945 HIVinfected patients attending the Harris County Hospital District in Houston, Texas. Twenty (87) of the HIV-infected patients diagnosed with Hodgkin lymphoma were receiving HAART and 3 (13) were naive to antiretroviral therapy. The incidence per 1,000 patients of Hodgkin lymphoma in patients receiving HAART was 6.5. The median duration of HAART before the diagnosis of Hodgkin lymphoma was 16 months (range, 7–22 mo). The median CD4 cell count was 235 cells/mm3(range, 189–325 cells/mm3) for the 20 HIV-infected patients receiving HAART at the time of diagnosis of Hodgkin lymphoma and 90 cells/mm3(range, 72–120 cells/mm3) for the 3 patients naive for antiretroviral therapy. Among patients with Hodgkin lymphoma receiving HAART, 50 (10/20) had an HIV-RNA viral load in plasma below the level of detection <400 copies/mL). Chemotherapy was administered to all patients, but a complete response was achieved in 30 (6/20) of the patients receiving HAART and 0 (0/3) of the patients naive to antiretroviral therapy. These results suggest that Hodgkin lymphoma has a low incidence in HIV-infected patients receiving HAART, but the malignancy is an aggressive disease with unfavorable clinical outcome in these patients.

Background & Aims:: Type 1 hepatorenal syndrome (HRS) is a severe complication of cirrhosis associated with a short median survival time (<2 weeks). Although the administration of terlipressin improves renal function, its effect on survival is unknown. This study investigated predictive factors of survival in patients with type 1 HRS treated with terlipressin. Methods:: Ninety-nine patients with type 1 HRS treated with terlipressin in 24 centers were retrospectively studied. Terlipressin-induced improved renal function was defined as a decrease in serum creatinine value to <130 @mmol/L or a decrease of at least 20% at the end of treatment. Results:: At inclusion, the Child-Pugh score was 11.8 +/- 1.6 (mean +/- SD). Terlipressin (3.2 +/- 1.3 mg/day) was administered for 11 +/- 12 days. Renal function improved in 58% of patients (serum creatinine decreased by 46% +/- 17% from 272 +/- 114 @mmol/L). Median survival time was 21 days. Survival rate was 40% at 1 month. Multivariate analysis showed that improved renal function and Child-Pugh score <11 at inclusion were independent predictive factors of survival (P < 0.0001 and 0.02, respectively). Thirteen patients underwent liver transplantation (92 +/- 95 days after HRS onset), 10 of whom had received terlipressin and had had improved renal function. Conclusions:: This retrospective uncontrolled study shows that in patients with type 1 HRS, terlipressin-induced improved renal function is associated with an increase in survival. Thus, a randomized trial investigating the effect of terlipressin on survival in patients with type 1 HRS should be performed.

The introduction of triple antiretroviral therapy has led to reductions in opportunistic diseases in HIV-infected patients. However, little is known of the effect of this therapy on the clinical and pathological features and the outcome of patients with AIDS-related systemic non-Hodgkin's lymphoma (NHL). We examined the incidence and clinical manifestations of HIV-infected patients with systemic NHL at the Harris County Hospital District and Veterans Affairs Medical Center (Houston, TX). Between January 1996 and December 2000, 76 cases of systemic NHL were diagnosed in 3655 HIV-infected patients. Three groups of patients diagnosed with systemic NHL were identified according to their history of antiretroviral therapy: treatment naive (n = 20), dual nucleoside (n = 22), and triple antiretroviral drug-treated patients (n = 34). The median duration of antiretroviral therapy before the diagnosis of systemic NHL in the triple antiretroviral and dual nucleoside treatment groups was 12 versus 8 months (p < 0.0004). Thirty-five percent of patients (12 of 34) in the triple treatment group had an HIV RNA viral load of <400 copies/ml and their median CD4+ cell count was 301 cells/mm3 (range, 46 to 667 cells/mm3) at the time of diagnosis of systemic NHL. More patients treated with triple antiretroviral therapy received complete courses of chemotherapy as compared with the other two groups (p = 0.013). However, the overall survival did not differ significantly among the three groups of patients. These data suggest that AIDS-related systemic NHL continues to occur even in patients treated with triple antiretroviral therapy. In addition, this opportunistic malignancy is associated with significant mortality. Therefore, it is necessary to develop a better understanding of the pathogenesis of this disease.

ABSTRACTA lymphotropic papovavirus (LPV) archetypal regulatory region was amplified from DNA from the blood of an immunocompromised rhesus monkey. We believe this is the first nonserological evidence of LPV infection in rhesus monkeys.

In this study, we characterized three full-length genome sequences with a similar mosaic structure from epidemiologically unlinked individuals from Cameroon (97CM-MP818) and the Central African Republic (99CF-MP1298 and 99CF-MP1307). Phylogenetic and recombinant analysis confirmed that the three strains had a similar complex recombinant genome, which we can designate now as CRF11-cpx. This new CRF was composed of successive fragments of subtype A, G, J, and CRF01-AE. The previously reported GR17 virus from a Greek patient infected in the Democratic Republic of Congo (DRC) has a similar structure and should be considered as the prototype strain of CRF11-cpx. This new CRF circulates in Cameroon, Central African Republic, Gabon, and DRC, although the exact prevalences remain to be determined.

The regulatory region (RR) of simian virus 40 (SV40) contains enhancer/promoter elements and an origin of DNA replication. Natural SV40 isolates from simian brain or kidney tissues typically have an archetypal RR arrangement with a single 72-basepair enhancer element. A rare simpler, shorter SV40 RR exists that lacks a duplicated sequence in the G/C-rich region and is termed protoarchetypal. Occasionally, SV40 strain variants arise de novothat have complex RRs, which typically contain sequence reiterations, rearrangements, and/or deletions. These variants replicate faster and to higher titers in tissue culture; we speculate that such faster-growing variants were selected when laboratory strains of SV40 were initially recovered. SV40 strains with archetypal RRs have been found in some human brain tumors. The possible implications of these findings and a brief review of the SV40 RR structure are presented.

We have used Leginon, a fully automatic system capable of acquiring cryo-electron micrographs, to collect data of single particles, specifically of the AAA ATPase p97. The images were acquired under low-dose conditions and required no operator intervention other than the initial setup and periodic refilling of the cold-stage dewar. Each image was acquired at two different defocus values. Two-dimensional projection maps of p97 were calculated from these data and compared to results previously obtained using the conventional manual data collection methods to film. The results demonstrate that Leginon performs as well as an experienced microscopist for the acquisition of single-particle data. The general advantages of automation are discussed.

MICHAEL RICHTER. Ireland and Her Neighbours in the Seventh Century. New York: St Martin's Press, 1999. Pp. 256. $55.00 (US). Reviewed by Dáibhí Ó CróinínTIMOTHY BROOK and GREGORY BLUE, eds. China and Historical Capitalism: Genealogies of Sinological Knowledge. New York: Cambridge University Press, 1999. Pp. xii, 291. $64.95 (US). Reviewed by Gang DengANDREAS KIESEWETTER. Die Anfänge der Regierung König Karls II. von Anjou (1278–1295): Das Königreich Neapel, die Grafschaft Provence und der Mittelmeerraum zu Ausgang des 13. Jahrhunderts. Husum: Matthiesen Verlag, 1999. Pp. 650. DM 168.00. Reviewed by Jean DunbabinPETER JACKSON. The Delhi Sultanate: A Political and Military History. New York: Cambridge University Press, 1999. Pp. xx, 367. $64.95 (US). Reviewed by Jos GommansARND REITEMEIER. Auβenpolitik im Spätmittelalter: Die diplomatischen Beziehungen zwischen dem Reich und England, 1377–1422. Paderborn: Verlag Ferdinand Schöningh, 1999. Pp. 572. DM 98.00. Reviewed by Jens RöhrkastenTHOMAS H. B. SYMONS, ed., with the assistance of STEPHEN ALSFORD and CHRIS KITZAN. Meta Incognita: A Discourse of Discovery: Martin Frobisher's Arctic Expeditions, 1576–1578: Volume I. Pp. xlvi, 298; Volume II. Pp. vi, 299–636. Hull: Canadian Museum of Civilization, 1999. $45.00 (CDN) for set; paper. Reviewed by G. V. ScammellPIETER EMMER. The Dutch in the Atlantic Economy, 1580–1880: Trade, Slavery, and Emancipation. Aldershot and Brookfield: Ashgate, Variorum, 1998. Pp. xi, 283. $89.95 (US). Reviewed by B. W. HigmanNABIL MATAR. Turks, Moors, and Englishmen in the Age of Discovery. New York: Columbia University Press, 1999. Pp. xi, 268. $32.50 (US). Reviewed by Edhem EldemALAN FROST and JANE SAMSON, eds. Pacific Empires: Essays in Honour of Glyndwr Williams. Vancouver: University of British Columbia Press, 1999. Pp. xii, 334. $27.95 (CDN), paper. Reviewed by I. C. CampbellL. M. CULLEN. 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Reviewed by Simon BurrowsEMMA VINCENT MACLEOD. A War of Ideas: British Attitudes to the Wars against Revolutionary France, 1792–1802. Aldershot and Brookfield: Ashgate, 1998. Pp. viii, 240. $76.95 (US). Reviewed by J. E. CooksonKOSTAS P. KOSTIS, ed. Modern Banking in the Balkans and West-European Capital in the Nineteenth and Twentieth Centuries. Aldershot and Brookfield: Ashgate, 1999. Pp. vi, 255. $86.95 (US). Reviewed by Guy VanthemscheLATA MANI. Contentious Traditions: The Debate on Sati in Colonial India. Berkeley: University of California Press, 1998. Pp. xiv, 246. $18.00 (US), paper. Reviewed by Robert Eric FrykenbergKENNETH D. LEHMAN. Bolivia and the United States: A Limited Partnership. Athens and London: University of Georgia Press, 1999. Pp. xviii, 296. $20.00 (US), paper. Reviewed by William P. StedmanPETER BALDWIN. Contagion and the State in Europe, 1830–1930. New York: Cambridge University Press, 1999. Pp. xiii, 581. $69.95 (US). Reviewed by Paul SlackCHRISTOPHER SCHMIDT-NOWARA. Empire and Antislavery: Spain, Cuba, and Puerto Rico, 1833–1874. Pittsburgh: University of Pittsburgh Press, 1999. Pp. xiii, 239. $22.95 (US), paper. Reviewed by Franklin W. KnightDAVID WALKER. Anxious Nation: Australia and the Rise of Asia, 1850–1939. St Lucia: University of Queensland Press, 1999. Pp. xv,312. $29.95 (AUS), paper. Reviewed by Peter PhelpsFAREED ZAKARIA. From Wealth to Power: The Unusual Origins of America's World Role. Princeton: Princeton University Press, 1998. Pp. x, 199. $29.95 (US). Reviewed by Richard RosecranceECKARD MICHELS. Deutsche in der FremdenUgion, 1870–1965: Mythen und Realitäten. Paderborn: Verlag Ferdinand Schöningh, 1999. Pp. 362. DM 68.00. Reviewed by Geoffrey WawroRAYMOND E. DUMETT. El Dorado in West Africa: The Gold-Mining Frontier, African Labor, and Colonial Capitalism in the Gold Coast, 1875–1900. Athens: Ohio University Press, 1998. Pp. xviii, 396. $19.95 (US)> paper; DIANE FROST. Work and Community among West African Migrant Workers since the Nineteenth Century. Liverpool: Liverpool University Press, 1999; dist. Portland: ISBS. Pp. 278. $44.95 (US). Reviewed by Ray A. KeaPAUL CHARLES MERKLEY. The Politics of Christian Zionism, 1891–1948. London and Portland: Frank Cass, 1998. Pp. x, 223. $52.50 (US), cloth; $24.50 (US), paper. Reviewed by Rory MillerAMIRA SONBOL, trans, and ed. The Last Khedive of Egypt: Memoirs of Abbas Hilmi II. Reading: Ithaca Press, 1998. Pp. xiii,390. $45.00 (US). Reviewed by Israel GershoniFRANCIS ANTHONY BOYLE. Foundations of World Order: The Legalist Approach to International Relations (1898–1922). Durham, NC and London: Duke University Press, 1999. Pp. ix, 220. $18.95 (US), paper. Reviewed by Eileen ScullyDAVID WOLFF. To the Harbin Station: The Liberal Alternative in Russian Manchuria, 1898–1914. Stanford: Stanford University Press, 1999. Pp. xiv, 255. $49.50 (US). Reviewed by R. Edward GlatfelterROBERT BICKERS. Britain in China: Community, Culture, and Colonialism, 1900–1949. Manchester: Manchester University Press, 1999; dist. Vancouver: University of British Columbia Press. Pp. xii, 276. £45.00. Reviewed by D. W. ClaytonSUSAN STRASSER, CHARLES MCGOVERN, and MATTHIAS JUDT, eds. Getting and Spending: European and American Consumer Societies in the Twentieth Century. New York: Cambridge University Press, 1998. Pp. xiv, 477. $59.95 (US), cloth; $21.95 (US), paper. Reviewed by Joy ParrJOANNA BOURKE. An Intimate History of Killing: Face-to-Face Killing in Twentieth-Century Warfare. New York: Basic Books, 1999. Pp. xxiii, 509. $30.00 (US). Reviewed by S. P. MacKenzieNICHOLAS A. LAMBERT. Sir John Fisher's Naval Revolution. Columbia: University of South Carolina Press, 1999. Pp. xvi, 410. $39.95 (US). Reviewed by C. I. HamiltonSUSAN R. GRAYZEL. Women's Identities at War: Gender, Motherhood, and Politics in Britain and France during the First World War. Chapel Hill and London: University of North Carolina Press, 1999; dist. Toronto: Scholarly Book Services. Pp. xix, 334. $32.95 (CDN), paper. Reviewed by Margaret R. HigonnetTRUDI TATE. Modernism, History, and the First World War. Manchester: Manchester University Press, 1998; dist. Vancouver: University of British Columbia Press. Pp. vii, 196. $27.95 (US)> paper. Reviewed by Robert L. NelsonSTÉPHANE COURTOIS, NICOLAS WERTH, JEAN-LOUIS PANNÉ, ANDRZEJ PACZKOWSKI, KAREL BARTOŠEK, and JEAN-LOUIS MARGOLIN, eds. The Black Book of Communism: Crimes, Terror, Repression, trans. Jonathan Murphy and Mark Kramer. Cambridge, Mass, and London: Harvard University Press, 1999. Pp. xx, 858. $37.50 (US). Reviewed by Peter KonecnyCECELIA LYNCH. Beyond Appeasement: Interpreting Interwar Peace Movements in World Politics. Ithaca and London: Cornell University Press, 1999. Pp. xi, 238. $32.50 (US). Reviewed by James HintonPHILIPP HEYDE. Das Ende der Reparationen: Deutschland, Frankreich und der Youngplan, 1929–1932. Paderborn: Verlag Ferdinand Schöningh, 1998. Pp. 506. DM 128.00. Reviewed by Andrew J. CrozierB. J. C MCKERCHER. Transition of Power: Britain's Loss of Global Pre-eminence to the United States, 1930–1945. New York: Cambridge University Press, 1999. Pp. xii, 403. $64.95 (US). Reviewed by Warren F. KimballSTEFAN HELL. Der Mandschurei-Konflikt: Japan, China und der Völkerbund, 1931 bis 1933. Tübingen: Universitas Verlag Tübingen, 1999. Pp. 285. DM 48.00, paper. Reviewed by Manfred JonasTHOMAS W. ZEILER. Free Trade, Free World: The Advent of GATT. Chapel Hill and London: University of North Carolina Press, 1999. Pp. xii, 267. $39.95 (US). Reviewed by Emily S. RosenbergROBERT STRADLING. The Irish and the Spanish Civil War, 1936–39: Crusades in Conflict. Manchester: Mandolin, 1999; dist. New York: St Martin's Press. Pp. xi, 288. $79.95 (US); FEARGHAL MCGARRY. Irish Politics and the Spanish Civil War. Cork: Cork University Press, 1999. Pp. 326. IR £45.00, cloth; IR £15.95, paper. Reviewed by Antonio Cazorla-SánchezYOSSI KATZ. Partner to Partition: The Jewish Agency's Partition Plan in the Mandate Era. London and Portland: Frank Cass, 1998. Pp. xii, 209. $49.50 (US), cloth; $24.50 (US), paper. Reviewed by Motti GolaniMICHAEL DOCKRILL. British Establishment Perspectives on France, 1936–40. New York: St Martin's Press, 1999. Pp. xiii, 212. $65.00 (US). Reviewed by John CharmleyMICHAEL JABARA CARLEY. 1939: The Alliance That Never Was and the Coming of World War II. Chicago: Ivan R. Dee, 1999. Pp. xxv, 321. $28.95 (US). Reviewed by Talbot ImlayDAVID M. GLANTZ. Zhukov's Greatest Defeat: The Red Army's Epic Disaster in Operation Mars, 1942. Lawrence: University Press of Kansas, 1999. Pp. x, 421. $39.95 (US). Reviewed by Mary R. HabeckWILLIAM I. HITCHCOCK. France Restored: Cold War Diplomacy and the Quest for Leadership in Europe, 1944–1954. Chapel Hill and London: University of North Carolina Press, 1998. Pp. xii, 291. $18.95 (US), paper. Reviewed by Anne DeightonKEES BOTERBLOEM. Life and Death under Stalin: Kalinin Province, 1945–1953. Montreal and Kingston: McGill-Queen's University Press, 1999. Pp. xxv, 435. $49.95 (CDN). Reviewed by J. Arch GettyCAROLINE WIEDMER. The Claims of Memory: Representations of the Holocaust in Contemporary Germany and France. Ithaca: Cornell University Press, 1999. Pp. x, 244. $39.95 (US). Reviewed by R. J. B. BosworthCOSTAS MELAKOPIDES. Pragmatic Idealism: Canadian Foreign Policy, 1945–1995. Montreal and Kingston: McGill-Queen's University Press, 1998. Pp. viii, 241. $39.95 (CDN). Reviewed by John EnglishPAOLO TRIPODI. The Colonial Legacy in Somalia: Rome and Mogadishu: From Colonial Administration to Operation Restore Hope. New York: St Martin's Press, 1999. Pp. xiv, 219. $72.00 (US). Reviewed by I. M. LewisYONG-PYO HONG. State Security and Regime Security: President Syngman Rhee and the Insecurity Dilemma in South Korea, 1953–60. New York: St Martin's Press, 2000. Pp. x, 219. $65.00 (US). Reviewed by William StueckROBERT R. BOWIE and RICHARD H. IMMERMAN. Waging Peace: How Eisenhower Shaped an Enduring Cold War Strategy. New York: Oxford University Press, 1998. Pp. x, 317. $74.95 (CDN); RICHARD H. IMMERMAN. John Foster Dulles: Piety, Pragmatism, and Power in US Foreign Policy. Wilmington: Scholarly Resources, 1999. Pp. xxvi, 221. $17.95 (US), paper. Reviewed by James L. GormlyPHILIP MURPHY. Alan Lennox-Boyd: A Biography. London and New York: I. B. Tauris, 1999; dist. New York: St Martin's Press. Pp. xi, 276. $39.50 (US). Reviewed by John RamsdenDONALD R. CULVERSON. Contesting Apartheid: US Activism, 1960–1987. Boulder: Westview Press, 1999. Pp. viii, 177. $75.00 (US). Reviewed by Thomas BorstelmannSTEPHEN G. RABE. The Most Dangerous Area in the World: John F. Kennedy Confronts Communist Revolution in Latin America. Chapel Hill and London: University of North Carolina Press, 1999. Pp. 257. $17.95 (US), paper. Reviewed by Stephen J. RandallJUDITH A. KLINGHOFFER. Vietnam, Jews, and the Middle East: Unintended Consequences. New York: St Martin's Press, 1999. Pp. xi, 232. $45.00 (US). Reviewed by Peter L. HahnROBERT K. BRIGHAM. Guerrilla Diplomacy: The NLF's Foreign Relations and the Viet Nam War. Ithaca and London: Cornell University Press, 1999. Pp. xviii, 215. $35.00 (US); ROBERT J. MCMAHON. The Limits of Empire: The United States and Southeast Asia since World War II. New York: Columbia University Press, 1999. Pp. xii, 276. $20.00 (US), paper. Reviewed by Philip E. CattonDOUGLAS A. BORER. Superpowers Defeated: Vietnam and Afghanistan Compared. London and Portland: Frank Cass, 1999. Pp. xxiii, 261. $57.50 (US), cloth; $26.50 (US), paper. Reviewed by Odd Arne WestadANDRÉ SZÁSZ. The Road to European Monetary Union. New York: St Martin's Press, 1999. Pp. xiii, 258. $69.95 (US). Reviewed by Scott LucasKENNETH W. STEIN. Heroic Diplomacy: Sadat, Kissinger, Carter, Begin, and the Quest for Arab-Israeli Peace. London and New York: Routledge, 1999. Pp. xix, 324. $24.99 (US), paper. Reviewed by William B. QuandtSTEPHEN J. MORRIS. Why Vietnam Invaded Cambodia: Political Culture and the Causes of War. Stanford: Stanford University Press, 1999. Pp. xiii, 315. $49.50 (US). Reviewed by Carlyle A. ThayerSTUART CROFT, JOHN REDMOND, G. WYN REES, and MARK WEBBER. The Enlargement of Europe. Manchester: Manchester University Press, 1999; dist. Vancouver: University of British Columbia Press. Pp. xv, 188. £40.00. Reviewed by Bo PeterssonTORBJØRN L. KNUTSEN. The Rise and Fall of World Orders. Manchester: Manchester University Press, 1999; dist. Vancouver: University of British Columbia Press. Pp. x, 324. $24.95 (US): paper. Reviewed by William R. ThompsonMARK PECENY. Democracy at the Point of Bayonets. University Park: Pennsylvania State University Press, 1999. Pp. xiii, 254. $18.95 (US), paper. Reviewed by David P. ForsytheTHOMAS R. MOCKAITIS. Peace Operations and Intrastate Conflict: The Sword or the Olive Branch?Westport: Praeger, 1999. Pp. xii, 166. $55.00 (US). Reviewed by Paul F. DiehlROBERT MANDEL. Deadly Transfers and the Global Playground: Transnational Security Threats in a Disorderly World. Westport: Praeger, 1999. Pp. xiv, 139. $55.00 (US). Reviewed by Frederic S. PearsonLUCIAN M. ASHWORTH and DAVID LONG, eds. New Perspectives on International Functionalism. New York: St Martin's Press, 1999. Pp. xiv, 181. $65.00 (US). Reviewed by Margaret P. KarnsZACHARY SELDEN. Economic Sanctions as Instruments of American Foreign Policy. Westport: Praeger, 1999. Pp. x, 147. $49.95 (US). Reviewed by William H. KaempferJOANNE GOWA. Ballots and Bullets: The Elusive Democratic Peace. Princeton: Princeton University Press, 1999. Pp. xii, 136. $27.50 (US). Reviewed by Randolph M. Siverson

The RNA and DNA tumor viruses have made fundamental contributions to two major areas of cancer research. Viruses were vital, first, to the discovery and analysis of cellular growth control pathways and the synthesis of current concepts of cancer biology and, second, to the recognition of the etiology of some human cancers. Transforming retroviruses carry oncogenes derived from cellular genes that are involved in mitogenic signalling and growth control. DNA tumor viruses encode oncogenes of viral origin that are essential for viral replication and cell transformation; viral oncoproteins complex with cellular proteins to stimulate cell cycle progression and led to the discovery of tumor suppressors. Viral systems support the concept that cancer development occurs by the accumulation of multiple cooperating events. Viruses are now accepted as bona fide etiologic factors of human cancer; these include hepatitis B virus, Epstein–Barr virus, human papillomaviruses, human T-cell leukemia virus type I and hepatitis C virus, plus several candidate human cancer viruses. It is estimated that 15% of all human tumors worldwide are caused by viruses. The infectious nature of viruses distinguishes them from all other cancer-causing factors; tumor viruses establish long-term persistent infections in humans, with cancer an accidental side effect of viral replication strategies. Viruses are usually not complete carcinogens, and the known human cancer viruses display different roles in transformation. Many years may pass between initial infection and tumor appearance and most infected individuals do not develop cancer, although immunocompromised individuals are at elevated risk of viral-associated cancers. Variable factors that influence viral carcinogenesis are reviewed, including possible synergy between viruses and environmental cofactors. The difficulties in establishing an etiologic role for a virus in human cancer are discussed, as well as the different approaches that proved viral links to cancer. Future directions for tumor virus studies are considered.

ABSTRACT“Clostridium neonatale” sp. nov., previously involved in an outbreak of neonatal necrotizing enterocolitis, was recently proposed as a new species of the Clostridiumgenus sensu stricto. We developed a one-step multiplex colony PCR for C. neonataleidentification and investigated C. neonataleintestinal colonization frequency in healthy preterm neonates.

The MDM2 oncoprotein encodes a 90 kDa nuclear phosphoprotein capable of abrogating the growth suppressive functions of p53 and pRb tumor suppressor proteins by direct interaction. Alternative splicing of MDM2 protein coding sequences has been documented during tumor progression in human ovarian and bladder carcinomas. The aim of this study was to determine whether alternative splicing of MDM2 occurs during breast tumorigenesis in mice and humans and whether protein coding sequences were affected. Specimens representing normal and malignant breast tissues from the murine D2 mammary tumor model system and human breast carcinomas were examined. Three distinct mdm2 mRNA transcripts of 3.3, 1.6 and 1.5 kb were detected in normal and malignant murine mammary tissues by Northern blot analysis using a full‐length mdm2cDNA probe. Additional Northern blot analysis using a probe derived from exon 12 of murine mdm2demonstrated that the 1.5 and 1.6 kb transcripts lack sequences encoding the C‐terminus of the protein. No evidence of internal deletions of protein coding sequences of mdm2 was detected in any of the normal mammary tissues or D2 murine mammary tumors examined by reverse transcription PCR (RT‐PCR). Three distinct MDM2 transcripts of 6.7, 4.7 and 1.9 kb were detected in malignant human breast tissue by Northern blot analysis using a cDNA probe specific for the complete open reading frame of human MDM2. However, a cDNA probe specific for the last exon of human MDM2hybridized only to the 6.7 and 4.7 kb transcripts, demonstrating that the 1.9 kb transcript lacked protein coding sequences contained in exon 12. Similarly, no internal deletions were detected in a panel of malignant human breast tissues using RT‐PCR and analogous primers within human MDM2. Therefore, breast tumors differ from other solid tumors reported previously in that no internal deletions of MDM2 protein coding sequences were observed. However, the data document the presence of multiple MDM2 mRNA transcripts in both normal and malignant breast tissues. A subset of MDM2 transcripts were shown to lack the last exon which contains sequences coding for the RING and zinc fingers and domains which are targets for caspase‐3 mediated proteolytic degradation and are required to target p53 for proteosomal degradation. Int. J. Cancer 81:292–298, 1999. © 1999 Wiley‐Liss, Inc.

Among the colonial powers of the early modern period, France was the last to emerge. Although, the French had not abstained from the exploration of fhe New World in the 16th century: G. de Verrazano discovered the site of New York (1524), during a voyage sponsored by King Francis I; Jacques Cartier sailed up the St. Lawrence to Quebec and Montreal (1535). From the early 16th century, many ships from ports such as Dieppe, St. Malo, La Rochelle, went on privateering and or trading expeditions to the Guinea coast, to Brazil, to the Caribbean, to the Spanish Main. Many French boats did fish off Newfoundland. Some traded in furs on the near-by Continent. Moreover, during the 16th century, sporadic attempts were made to establish French settlements in ?Equinoctial France? (Brazil), in Florida, in modern Canada, but they failed utterly. Undoubtedly, foreign wars against the Habsburgs, during the first half of the 16th and of the 17th centuries, civil ?wars of religion? during the second half of the 16th century, political disorders like the blockade of La Rochelle or the Frondeduring the first part of the 17th century, absorbed the attention and resources of French rulers, despite some ambitious projects, like those of Richelieu, for overseas trade. As for the port cities they tried to trade overseas but they were isolated and not strong enough (specially during die wars of religion) to create ?colonies?. Some small companies, which had been started in 1601 and 1604, to trade with the East Indies, were very short-lived, and the French did not engage seriously in Asian trade before 1664.

Authentic simian virus 40 (SV40) has been detected in association with human choroid plexus and ependymoma tumors, and SV40-like DNA sequences have been found in some human osteosarcomas. We report here an analysis of human osteosarcoma samples for the presence of SV40 DNA using PCR and primers directed at 4 distinct sites of the SV40 genome, coupled with sequence analysis. Authentic SV40 DNA sequences were detected in 5 of 10 osteosarcoma tumor samples. The SV40 regulatory region in each case was identical and of archetypal length (non-duplicated enhancer), as is usually found in natural isolates of SV40 from monkeys and in human brain tumors. A section of the gene that encodes a viral late gene product (VP1) was detected in 5 of 10 tumors and had an exact match with the known sequence of SV40. Two separated segments of the large T-antigen (T-ag) gene were found in the same 5 tumors. Analysis of the DNA sequences encoding the T-ag carboxy terminus revealed sequence variation among the tumors, as observed previously in viral DNA associated with human brain tumors. There does not appear to be a preferential association of a T-ag variable domain sequence with a given tumor type. No sequences from the regulatory region of human polyomaviruses JCV and BKV were detected in the bone tumors. We also noted less efficient recovery of SV40 DNA from tumor samples fixed in paraffin as compared to frozen tumors. Our results confirm the presence of SV40 DNA in human bone tumors and, based on the sequence variation observed for the carboxy terminus of the T-ag gene, suggest that there is not a specific SV40 strain associated with human osteosarcomas. Int. J. Cancer 72:791–800, 1997. © 1997 Wiley-Liss, Inc.

Nuclear microinjection of c-H-ras DNA induced DNA synthesis in reversibly nonproliferating quiescent human cells. The proto-oncogene and oncogene forms were equally effective inducers. In contrast, c-H-ras DNA either alone or in combination with the adenovirus E1A gene did not cause terminally nondividing senescent cells to synthesize DNA.

Expression of simian virus 40 T antigen (Tag) in the rod photoreceptors of transgenic mice leads to cell death that is completed by the end of the third week of postnatal development. To understand the mechanistic link between Tag expression and the death of the expressing photoreceptors, cell cycle activity was followed in a transgenic mouse family that expresses Tag directed by the mouse opsin promoter. Tag-expressing photoreceptors also expressed rhodopsin suggesting that these cells were differentiated. The presence of Tag in the photoreceptors induced the expression of both proliferating cell nuclear antigen (PCNA) and thymidine kinase (TK). The abnormally high levels of PCNA and TK continued until the complete disappearance of the cells expressing Tag. Photoreceptor cell death was also associated with continued DNA synthesis that ceased shortly after postnatal day 16. The specific loss of the rod photoreceptors that re-entered the cell cycle accounted entirely for the loss of photoreceptors from the outer nuclear layer. The antiproliferative nature of the mature retina is directly involved in the apoptotic death of photoreceptors expressing Tag.

Mouse, hamster, and human cells were transformed at the permissive temperature by mutants from simian virus 40 (SV40) complementation group A in order to ascertain the role of the gene A function in transformation. The following parameters of transformation were monitored with the transformed cells under permissive and nonpermissive conditions: morphology; saturation density; colony formation on plastic, on cell monolayers, and in soft agar; uptake of hexose; and the expression of SV40 tumor (T) and surface (S) antigens. Cells transformed by the temperature-sensitive (ts) mutants exhibited the phenotype of transformed cells at the nonrestrictive temperature for all of the parameters studied. However, when grown at the restrictive temperature, they were phenotypically similar to normal, untransformed cells. Growth curves showed that the (ts) A mutant-transformed cells exhibited the growth characteristics of wild-type virus-transformed cells at the permissive temperature and resembled normal cells when placed under restrictive conditions. There were 3-to 51-fold reductions in the levels of saturation density, colony formation, and uptake of hexose when the mutant-transformed cells were the elevated temperature as compared to when they were grown at the permissive temperature. Mutant-transformed cells from the nonpermissive temperature were able to produce transformed foci when shifted down to permissive conditions, indicating that the phenotypically reverted cells were still viable and that the reversion was a reversible event. SV40 T antigen was present in the cells at both temperatures, but S antigen was not detected in cells maintained at the nonpremissive temperature. All of the wild-type virus-transformed cells exhbited a transformed cells exhibited a transformed phenotype when grown under either restrictive or nonrestrictive conditions. Thers results indicate that the SV40 group A mutant-transformed cells are temperature sensitive for the maintenance of growth properties characteristics of transformation. Virus rescued from the mutant-transformed cells by the transfection method was ts, suggesting that the SV40 gene A function, rather than a cellular one, is responsible for the ts behavior of the cells.

An epithelial cell line, designated COMMA-1D, was derived from mammary tissue of BALB/c mice in the middle of pregnancy. This line, in continuous cell culture for 12 months, exhibits several characteristics distinctive of normal mammary epithelial cells, including induction of casein synthesis in vitro and normal duct morphogenesis in the cleared mammary fat pads of syngeneic mice. The cells also form domes in high density culture and are positive for keratin intermediate filaments by indirect immunofluorescence. COMMA-1D cells have a near diploid number of chromosomes and do not grow in suspension culture or produce tumors in syngeneic hosts. This cell line should prove useful for studies examining the regulation of normal cellular differentiation of mammary cells as well as transformation of epithelial cells to the preneoplastic and neoplastic phenotypes.