Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment.

Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P=0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.Leukemia advance online publication, 20 November 2015; doi:10.1038/leu.2015.281.

Obesity during pregnancy on vagal tone, hemoglobin A1c, oxygenation, and perinatal outcomes

Purpose: To examine the effect of obesity and gestational weight gain on heart rate variability (HRV), oxygenation (HbO 2 and SpO2), hemoglobin A1c (HbA1c) and the frequency of pregnancy complications in obese (O) and non-obese (NO) women.^ Design: The study was an observational comparison study with a repeated measures design. ^ Setting: The setting was a low risk prenatal, university clinic located in a large southeastern metropolitan city. ^ Sample: The sample consisted of a volunteer group of 41 pregnant women who were observed at the three time points of 20, 28, and 36 weeks gestation. ^ Analysis: Analysis included general linear modeling with repeated measures to test for group differences with changes over time on vagal response, HbA1c, and oxygenation. Odds ratios were computed to compare the frequency of birth outcomes. ^ Findings: The interaction effect of time between O and NO women on HbO2 was significant. The mean HP, RSA, and HbO2 changed significantly over time within the NO women. The mean HbA 1c increased significantly over time within the O women. Women with excess gestational weight gain had significantly lower heart period than women with weight gain within the IOM recommendations. Obese women were more likely to have Group B streptococcal infections, gestational hypertension, give birth by cesarean or instrument assistance, and have at least one postnatal event. ^ Conclusions: Monitoring HRV, oxygenation, and HbA1c using minimally invasive measures may permit early identification of alterations in autonomic response. Implementation of interventions to promote vagal tone may help to reduce risks for adverse perinatal outcomes related to obesity. Future studies should examine the effect of obesity on the vagal response and perinatal outcomes. ^

Secondary left ventricular ejection fraction response to beta blocker therapy in heart failure patients

Chronic β-blocker treatment improves survival and left ventricular ejection fraction (LVEF) in patients with systolic heart failure (HF). Data on whether the improvement in LVEF after β-blocker therapy is sustained for a long term or whether there is a loss in LVEF after an initial gain is not known. Our study sought to determine the prevalence and prognostic role of secondary decline in LVEF in chronic systolic HF patients on β-blocker therapy and characterize these patients. Retrospective chart review of HF hospitalizations fulfilling Framingham Criteria was performed at the MEDVAMC between April 2000 and June 2006. Follow up vital status and recurrent hospitalizations were ascertained until May 2010. Three groups of patients were identified based on LVEF response to beta blockers; group A with secondary decline in LVEF following an initial increase, group B with progressive increase in LVEF and group C with progressive decline in LVEF. Covariate adjusted Cox proportional hazard models were used to examine differences in heart failure re-hospitalizations and all cause mortality between the groups. Twenty five percent (n=27) of patients had a secondary decline in LVEF following an initial gain. The baseline, peak and final LVEF in this group were 27.6±12%, 40.1±14% and 27.4±13% respectively. The mean nadir LVEF after decline was 27.4±13% and this decline occurred at a mean interval of 2.8±1.9 years from the day of beta blocker initiation. These patients were older, more likely to be whites, had advanced heart failure (NYHA class III/IV) more due to a non ischemic etiology compared to groups B & C. They were also more likely to be treated with metoprolol (p=0.03) compared to the other two groups. No significant differences were observed in combined risk of all cause mortality and HF re-hospitalization [hazard ratio 0.80, 95% CI 0.47 to 1.38, p=0.42]. No significant difference was observed in survival estimates between the groups. In conclusion, a late decline in LVEF does occur in a significant proportion of heart failure patients treated with beta blockers, more so in patients treated with metoprolol.^

Impact of BCR -ABL on DNA repair

The BCR-ABL fusion gene is the molecular hallmark of Philadelphia-positive leukemias. Normal Bcr is a multifunctional protein, originally localized to the cytoplasm. It has serine kinase activity and has been implicated in cellular signal transduction. Recently, it has been reported that Bcr can interact with xeroderma pigmentosum group B (XPB/ERCC3)—a nuclear protein active in UV-induced DNA repair. Two major Bcr proteins (p160 Bcr and p130Bcr) have been characterized, and our preliminary results using metabolic labeling and immunoblotting demonstrated that, while both the p160 and p130 forms of Bcr localized to the cytoplasm, the p130 form (and to a lesser extent p160) could also be found in the nucleus. Furthermore, electron microscopy confirmed the presence of Bcr in the nucleus and demonstrated that this protein associates with metaphase chromatin as well as condensed interphase heterochromatin. Since serine kinases that associate with condensed DNA are often cell cycle regulatory, these observations suggested a novel role for nuclear Bcr in cell cycle regulation and/or DNA repair. However, cell cycle synchronization analysis did not demonstrate changes in levels of Bcr throughout the cell cycle. Therefore we hypothesized that BCR serves as a DNA repair gene, and its function is altered by formation of BCR-ABL. This hypothesis was investigated using cell lines stably transfected with the BCR-ABL gene, and their parental counterparts (MBA-1 vs. M07E and Bcr-AblT1 vs. 4A2+pZAP), and several DNA repair assays: the Comet assay, a radioinimunoassay for UV-induced cyclobutane pyrimidine dimers (CPDs), and clonogenic assays. Comet assays demonstrated that, after exposure to either ultraviolet (UV)-C (0.5 to 10.0 joules m −2) or to gamma radiation (200–1000 rads) there was greater efficiency of DNA repair in the BCR-ABL-transfected cells compared to their parental controls. Furthermore, after UVC-irradiation, there was less production of CPDs, and a more rapid disappearance of these adducts in BCR-ABL-bearing cells. UV survival, as reflected by clonogenic assays, was also greater in the BCR-ABL-transfected cells. Taken together, these results indicate that, in our systems, BCR-ABL confers resistance to UVC-induced damage in cells, and increases DNA repair efficiency in response to both UVC- and gamma-irradiation. ^

Significado de la Leucopenia en pacientes con bacteriemia

Objetivo: Evaluar parámetros clínicos, bacteriológicos y morbimortalidad de las bacteriemias en pacientes con leucopenia (<4.000 leucocitos/mm 3) y compararlas con bacteriemias con leucocitosis (>12.000/mm3). Material y métodos: Estudio protocolizado, descriptivo y observacional en pacientes con 2 o más hemocultivos positivos para el mismo germen hospitalizados en un servicio de clínica médica desde Marzo de 1989 a Agosto de 2007. Resultados: Se identificaron 728 bacteriemias, 94 (12,91%) con leucopenia (Grupo A) y 407 (55,90%) con leucocitosis (Grupo B). La edad media fue de 55,57 años (DS±16,93) en A y de 58,40 años (DS±17,34) en B. No hubo diferencias en la permanencia media: 19,59 días (DS±18,67) en A vs 21,21 (DS±19,53) en B ni en el sexo masculino (65,96 vs 57,25%)(pNS). La adquisición nosocomial (57,44 vs 40,29%) y el foco desconocido (25,53 vs 9,33%) y abdominal (17,14 vs 9,21%) fueron más frecuentes en A (p<0.01). La comorbilidad mayor (82,98 vs 41,24%), neoplasias (45,74 vs 12,84%) y la inmunosupresión (31,91 vs 6,17%) fueron significativas en A (p<0.01). La anemia (86,17 vs 62,40%) y la trombocitopenia (84,04 vs 25,06%) predominaron en A (p<0.01). Los Bacilos Gram Negativos predominaron en A (61,71 vs 37,83%)(p<0.01) [Klebsiella (17,02 vs 9,82%) y Pseudomonas (10,64 vs 1,47%) las más frecuentes (p<0.05)] y en B fue más frecuente S. aureus (31,69 vs 11,70%)(p<0.01). La mortalidad fue de 39,36% en A y 25,30% en B (p=0.006) y se asoció en el grupo A a mayor mortalidad en las primeras 24 horas (32,43 vs 16,50%), inmunosupresión (27,02 vs 7,76%), neumococcemias (52,94 vs 23,07%), sepsis (100 vs 88,35%) y trombocitopenia (75,67 vs 30,09%)(p<0,01).- Conclusiones: Las bacteriemias en pacientes leucopénicos comparadas con aquellas con leucocitosis se asociaron significativamente a adquisición nosocomial, foco desconocido y abdominal, presencia de comorbilidad mayor, neoplasias e inmunosupresión, a bacteriemias por Klebsiella y Pseudomonas y a significativa mayor mortalidad. Palabras claves: leucopenia, bacteriemias

Bacteriemias en Mayores de 65 años : resultados de un análisis comparativo

Objetivos: Evaluar parámetros clínicos, bacteriológicos y morbimortalidad en pacientes mayores de 65 años con bacteriemia (Grupo A) y compararlos con aquellas ocurridas en menores de 65 años (grupo B) hospitalizados en un servicio de clínica médica. Material y métodos: Estudio protocolizado, descriptivo y observacional, desde 1989-2006. Criterios de inclusión: dos o más hemocultivos positivos. Análisis estadístico con Epi Info 6.4 . Resultados: Se identificaron 668 bacteriemias: 258 (38,6%) en A y 410 (61,4%) en B. La edad media fue de 74,2 años (DS±7.01) y de 47,2 años (DS±13.7) respectivamente. No hubo diferencias en la permanencia media: 19,1 días (DS±17.07) en A y 19,9 (DS±18,1) en B, ni en el origen nosocomial (40,7 vs 44%). Los focos pulmonar (31 vs 21,2%)(p<0,008) y urinario (27 vs 18,8%)(p=0.017) fue más frecuentes en A. La fiebre >de 38 ºC fue menos frecuente en A (83,8 vs 90,9%)(p=0.0068), mientras que la hipotensión arterial (40,8 vs 32,2%)(p=0.03), oliguria (41,7 vs 30,9%)(p=0.005) y encefalopatía (54,5 vs 39,4%)(p=0.00014) fueron mas comunes en A. Los bacilos gram negativos predominaron en A (46 vs 37%)(p<0.01) con diferencias entre A.baumani (9,16 vs 4,6%) y E.coli (54,1 vs 42,7%)(p<0.05) y en B fueron más frecuentes por S.aureus MS (34.39 vs 24,63)(p=0.01). El shock séptico (33,9 vs 22,4%) y nuevas insuficiencias de órganos (31,1 vs 20,1%) prevalecieron en A (p<0,001). La mortalidad fue de 34,49% para A y de 23,41% para B (p=0,018) Conclusiones: Las bacteriemias en pacientes internados mayores de 65 años comparadas con las ocurridas en pacientes. de menor edad, se caracterizaron significativamente por tener predominio del foco pulmonar y urinario, de hipotensión arterial, oliguria y encefalopatía, de bacteriemia por BGN, principalmente A. baumanii y E. coli; mayor desarrollo de shock séptico, menor frecuencia de fiebre >38°C y de bacteriemia por MSS A, y significativa mayor mortalidad.

Estado funcional y mortalidad en pacientes neoplásicos hospitalizados

Objetivos: Analizar el estado funcional y su relación con morbimortalidad en pacientes con neoplasias internados en Cínica Médica. Material y métodos: Estudio descriptivo, protocolizado y observacional. Se analizaron variables clínicas, estado funcional, situación anímica y morbimortalidad en pacientes oncológicos hospitalizados y se compararon pacientes con Índice de Karnofsky <40 puntos (grupo A) y >40 puntos (grupo B). Los datos fueron analizados en EPI Info 6.04. Informe de los primeros 3 meses. Resultados: En el período de estudio, ingresaron 66 pacientes con neoplasias, 21 (31.8%) en A, con Karnofsky promedio de 25 puntos (DS±12.09) y 45 (68.2%) en B, con Karnofsky promedio de 77 puntos (DS±16.65). El 77.3% presentó tumores sólidos y el 22.7% hematológicos y las neoplasias más frecuentes fueron del tracto gastrointestinal (19.6%), mama (12.1%), pulmón (9.1%) y primario oculto (7.6%). El estadio tumoral IV fue el más frecuente en ambos grupos (89.5% de A y 88.9% de B)(pNS). La edad media en A fue de 59.57 (DS±13.71) y 52.48 años (DS±15.65) en B (pNS) y el género masculino fue más frecuente en A (66.7 y 44.4% respectivamente) (p<0.05). La permanencia media fue de 17.57 en A (DS±20.84) y de 13.53 días (DS±16.29) en B (pNS). La evaluación de Actividades Básicas de la Vida Diaria [0.81 (DS±1.25) vs 4.57 puntos (DS±1.15)] y Actividades Instrumentales [0.57 (DS±0.74) vs 4 puntos (DS±1.37)] fue superior en B (p<0.05) y no hubo diferencias en la comorbilidad (85.7 vs 82.2%)(pNS). Las infecciones (52.4 vs 26.7%), causa social (38.1 vs 4.4%), complicaciones neoplásicas (81 vs 51.1%) y dolor (81 vs 51.1%) fueron los motivos de internación más frecuentes en A (p<0.05). Los pacientes de A recibieron con mayor frecuencia cuidados paliativos (90.5 vs46.7%) y quimioterapia (90.5 vs 46.7%)(p<0.05), sin diferencias en radioterapia (23.8 vs 13.3%) y cirugía (33.3 vs 33.3%)(pNS). No hubo diferencias entre ambos grupos en la presencia de depresión clínica (69.9 vs 53.3%) y pérdida de peso (86.4 vs 84.2%)(pNS). El síndrome confusional (85.7 vs 11.1%), postración (61.9 vs 6.7%) y escaras (23.8 vs 4.4%) fueron más frecuentes en A (p<0.05). La mortalidad hospitalaria fue 52.4% en A y 8.9% en B (p<0.05). Conclusiones: El grado de estado funcional evaluado por Karnofsky menor de 40 puntos se asoció significativamente a: mayor mortalidad, uso de quimioterapia, cuidados paliativos, internación por infecciones, dolor y complicaciones neoplásicas y presencia de síndrome confusional, postración y escaras de decúbito (p<0.05).

The petrology of the lower series volcanics of ODP Hole 104-642E

Between 1086.6 and 1229.4 m below seafloor at Site 642 on the Outer Vøring Plateau, a series of intermediate volcanic extrusive flow units and volcaniclastic sediments was sampled. A mixed sequence of dacitic subaerial flows, andesitic basalts, intermediate volcaniclastics, subordinate mid-ocean ridge basalt, (MORB) lithologies, and intrusives was recovered, in sharp contrast to the more uniform tholeiitic T-type MORB units of the overlying upper series. This lower series of volcanics is composed of three chemically distinct groups, (B, A2, A1), rather than the two previously identified. Flows of the dacitic group (B) have trace-element and initial Sr isotope signatures which indicate that their source magma derived from the partial melting of a component of continental material in a magma chamber at a relatively high level in the crust. The relative proportions of crustal components in this complex melt are not known precisely. The most basic group (A2) probably represents a mixture of this material with MORB-type tholeiitic melt. A third group (A1), of which there was only one representative flow recovered, is chemically intermediate between the two groups above, and may suggest a repetition of, or a transition phase in, the mixing processes.

Lower Cretaceous dinoflagellate cysts of Exmouth Plateau, Nortwest Australia

Cores from Leg 122, Sites 762 and 763, were sampled at intervals of one sample per 1.5-m section in the Lower Cretaceous sequences. More than 400 samples were studied, most of which contained dinoflagellate cysts, spores, pollen, and various types of palynoclasts. From the entire palynomorph assemblage mainly dinoflagellate cysts were studied to give a stratigraphic outline for the Lower Cretaceous. Stratigraphic units were interpreted in terms of zones in use for the Jurassic and Cretaceous of Australia. At both sites a condensed Valanginian to Aptian sequence and an expanded middle to late Berriasian sequence containing a rich microplankton assemblage were recovered. Sites 762 and 763 can be correlated with each other and with the wells Eendracht-1 and Vinck-1.

Oligocene and Neogene radiolarians from the Labrador Sea

Two sites in the Labrador Sea and one site in Baffin Bay were drilled during Leg 105. Radiolarians were recovered at all three sites, although at Site 645 (Baffin Bay), radiolarians were present in useful numbers only in the mudline sample. Radiolarians of late Neogene age were recovered at Site 646 south of Greenland, while early Oligocene and early Miocene radiolarians were recovered from the Labrador Sea at Site 647. In Site 646, radiolarian and other coarse-fraction abundances vary dramatically from sample to sample and may reflect deep-water depositional processes as well as changes in surface-water conditions. Site 647 siliceous microfossils reach their peak abundance and preservation in Core 105-647A-25R and decline gradually upward into the lower Miocene (Cores 105-647A-13R and -14R). Siliceous microfossil abundances in counts of the > 38-µm Carbonate-free coarse fraction from the siliceous interval are correlated to each other, but not to the abundance of nonbiogenic coarse-fraction components. Radiolarian abundances in specimens per gram (but not diatom abundances) are correlated to bulk opal concentration and to the organic carbon content of the sediment. The abundance of radiolarians and other siliceous microfossils within the lower Oligocene to lower Miocene is interpreted as reflecting changes in surface-water productivity. With only a few exceptions, no stratigraphic indicator species were seen in samples from either Site 646 or Site 647. The absence of both tropical/subtropical and Norwegian-Greenland Sea stratigraphic forms is due to the dominance of subarctic North Atlantic taxa in Leg 105 assemblages. The early Oligocene and early Miocene assemblages recovered at Site 647 are of particular interest, as very little material of these ages has previously been recovered from the subarctic North Atlantic region, and virtually no descriptive work has been conducted on the more endemic components of the radiolarian assemblages from these time intervals. Thus, this report concentrates on providing, at least in part, the first comprehensive documentation of early Oligocene and early Miocene radiolarians from the subarctic North Atlantic, with emphasis on basic descriptions, measurements, and photographic documentation. However, synonymic work and formal designation of new species names has been deferred until additional material from other regions can be examined. The sole exception is the emendation of Theocalyptra tetracantha Bjorklund and Kellogg 1972 to Cycladophora tetracantha n. comb.

Mineralogical and geochemical analyses of serpentines from ODP Hole 125-778A

Thirty-five samples from Hole 778A were prepared for X-ray diffraction (XRD) mineralogical analyses and for chemical analyses of major and trace elements. Most of the selected samples were silt- and sand-sized sedimentary serpentinites or microbreccias except for a soft clast of mafic rock, a hard clast of massive serpentinized peridotite, and a pebble of consolidated, undeformed serpentine microbreccia that contained planktonic foraminifers. Both mineralogical and geochemical analyses allow discrimination of three groups among the analyzed samples. These groups correspond to three stratigraphic intervals present along the drilled section. Group A contains the upper samples (lithologic Unit I). These consist of poorly consolidated serpentine muds carrying hard-rock clasts (serpentinized peridotites, metabasalts). They are characterized by the following mineralogical assemblage: serpentine, Fe-oxides and hydroxides, aragonite, and halite. They exhibit variable SiO2, MgO contents, but are characterized by a SiO2/MgO ratio near 1. CaO content is high in relation to development of aragonite. Al2O3 content is low. Relatively high K2O, Na2O, and Sr contents are present, presumably in relation to interactions with seawater. Group B (30-77 mbsf) contains samples exhibiting very homogeneous chemical and mineralogical compositions. They consist of serpentinite microbreccias exhibiting frequent shear structures. Hard-rock clasts are also present (serpentinized peridotites, metabasalts, one possible chert fragment). The mineralogy of the Group B samples is characterized by the presence of serpentine and authigenic minerals: hydroxycarbonates and hydrogrossular. Calcite and chlorite are also present, but all the samples lack aragonite. Their chemical compositions are remarkably similar to compositions of their parent rocks. Group C contains silt- and sand-sized serpentine and serpentine microbreccias, which are locally rich in red clasts, probably strongly altered (oxidized?) mafic fragments. Intervals having clasts of more diverse origin than those higher in the section were recovered. Clast lithology includes serpentinized peridotites, metabasalts, metavolcaniclastite, meta-olivine gabbro, and amphibolite sandstone. Mineralogy and geochemistry reflect these compositions. Serpentine content of the samples is less than in previous groups. Correlatively, sepiolite, palygorskite, and chlorite-smectite are mineral phases present in the analyzed samples. Accessory igneous minerals (amphiboles, pyroxenes, hematite) also were found. The chemical compositions of most of Group C samples differ from that of massive serpentinized peridotites. The main differences are (1) higher SiO2, CaO, TiO2 and Al2O3 contents, (2) a SiO2/MgO ratio greater than 1, and (3) a negative correlation between Al2O3, and MgO, Cr, and Ni. These characteristics suggest new constraints relative to the flow structure of the flank of Conical Seamount.

Radiosonde profiles and meteorological observations during Atlantic Expedition M2 in 1965 (IQSY) of RV "Meteor"

A radiosonde is described for measuring the upward and downward fluxes of visible light in the atmosphere. Photoresistors are used as sensors, the optical center of the spectral range beeing at 0.55 µ. The results of these flux-measurements obtained during the Atlantic Expedition 1965 with the research vessel "Meteor" are presented. The datas have been divided into three groups according to the amount of cloudiness. In group a) (small cloudiness) the extinction coefficient of the prevailing linear radiation is derived as a function of the height. Characteristics of airmasses of maritime or continental origin are shown. In group b) (cloud covered sky) microphysical quantities are determined from the radiative lapse rate in the clouds. The average radius of droplets is found to lie between 5.5 µm and 14.4 µm. The albedo of cloud surfaces varies between 25% and 54%, the transmission values are between 58% and 73%. One ascent through a Cirrus cloud of considerable vertical thickness is treated seperately. The observed distribution of extinction is compared with theoretical values in water clouds leading to the same order of magnitude. The relation between the albedo of the surface of the sea and the amount of cloudiness is discussed.

Investigations on seven sediment cores from the New Ireland Basin, east of Papua New Guinea

Sediment cores were recovered from the New Ireland Basin, east of Papua New Guinea, in order to investigate the late Quaternary eruptive history of the Tabar-Lihir-Tanga-Feni (TLTF) volcanic chain. Foraminifera d18O profiles were matched to the low-latitude oxygen isotope record to date the cores, which extend back to the early part of d18O Stage 9 (333 ka). Sedimentation rates decrease from >10 cm/1000 yr in cores near New Ireland to ~2 cm/1000 yr further offshore. The cores contain 36 discrete ash beds, mostly 1-8 cm thick and interpreted as either fallout or distal turbidite deposits. Most beds have compositionally homogeneous glass shard populations, indicating that they represent single volcanic events. Shards from all ash beds have the subduction-related pattern of strong enrichment in the large-ion lithophile elements relative to MORB, but three distinct compositional groups are apparent: Group A beds are shoshonitic and characterised by >1300 ppm Sr, high Ce/Yb and high Nb/Yb relative to MORB, Group B beds form a high-K series with MORB-like Nb/Yb but high Ce/Yb and well-developed negative Eu anomalies, whereas Group C beds are transitional between the low-K and medium-K series and characterised by flat chondrite-normalised REE patterns with low Nb/Yb relative to MORB. A comparison with published data from the TLTF chain, the New Britain volcanic arc and backarc including Rabaul, and Bagana on Bougainville demonstrates that only Group A beds share the distinctive phenocryst assemblage and shoshonitic geochemistry of the TLTF lavas. The crystal- and lithic-rich character of the Group A beds point to a nearby source, and their high Sr, Ce/Yb and Nb/Yb match those of Tanga and Feni lavas. A youthful stratocone on the eastern side of Babase Island in the Feni group is the most probable source. Group A beds younger than 20 ka are more fractionated than the older Group A beds, and record the progressive development of a shallow level magma chamber beneath the cone. In contrast, Group B beds represent glass-rich fallout from voluminous eruptions at Rabaul, whereas Group C beds represent distal glass-rich fallout from elsewhere along the volcanic front of the New Britain arc.

Ozonolysis for selectively depolymerizing polysaccharides containing β-d-aldosidic linkages

The depolymerization of polysaccharides, particularly those containing acid-sensitive components, into intact constituent repeating units can be very difficult. We describe a method using ozonolysis for depolymerizing polysaccharides containing β-d-aldosidic linkages into short-chain polysaccharides and oligosaccharides. This method is carried out on polysaccharides that have been fully acetylated whereby β-d-aldosidic linkages are selectively oxidized by ozone to form esters, from which the polysaccharides are subsequently cleaved with a nucleophile. Ozone oxidation of aldosidic linkages proceeds under strong stereoelectronic control, and reaction rates depend on the conformations of glycosidic linkages. Thus, β-d-aldosidic linkages with different conformations can have very different reaction rates even in the absence of substantial chemical differences. These rate differences allowed for very high selectivity in cleaving β-d-linkages of polysaccharides. Several polysaccharides from group B Streptococcus and other bacterial species were selectively depolymerized with this method. The repeating units of the group B Streptococcus polysaccharides all contain an acid-sensitive sialic acid residue in a terminal position on a side chain and several β-d-residues including galactose, glucose, and N-acetylglucosamine; however, with each polysaccharide, one type of linkage was more reactive than others. Selective cleavage of the most sensitive linkage occurs randomly throughout the polymer chain, yielding fragments of controllable and narrowly distributed sizes and the same repeating-unit structure. The average size of the molecules decreases exponentially, and desired sizes can be obtained by stopping the reaction at appropriate time points. With this method the labile sialic acid residue was not affected.