bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate of East Africa 6000 14C Yr B.P. as Inferred from Pollen Data
Authors: Peyron Odile , Jolly Dominique , Bonnefille Raymonde , Vincens Annie , Guiot Joël
Published: September 2002

This paper presents a spatial reconstruction of climate in East Africa at 6000 14C yr B.P. Two different approaches using pollen data have been used, the standard “best modern analogues” method and the new “plant functional type” method, based on groups of pollen taxa. Both methods have been applied to 32 fossil pollen spectra dated at 6000 14C yr B.P. For each site, we have estimated two climatic parameters (annual precipitation and mean annual temperature), three bioclimatic parameters (ratio of actual to potential evapotranspiration, and the mean temperature of the coldest and warmest months). Results show that the temperature lapse rate was less steep at 6000 14C yr B.P. than it is today. The climate was wetter north of 3°S (precipitation anomalies >+50 mm/yr) and slightly drier farther south (precipitation anomalies ≤+50 mm/yr). The ratio of actual to potential evapotranspiration also indicates conditions similar to or wetter than today north of 3°S (anomalies >10%). The climate was warmer than today by 2°C north of the equator and was cooler southward (≤−1°C). Although both methods indicate similar climatic patterns, the plant functional type method provides more consistent results.
Correlation between Vegetation in Southwestern Africa and Oceanic Upwelling in the Past 21,000 Years
Authors: Shi Ning , Dupont Lydie M. , Beug Hans-Jürgen , Schneider Ralph
Published: September 2002

Dinoflagellate cyst and pollen records from marine sediments off the southwestern African coast reveal three major aridification periods since the last glaciation and an environmental correlation between land and sea. Abundant pollen of desert, semi-desert, and temperate plants 21,000–17,500 cal yr B.P. show arid and cold conditions in southwestern Africa that correspond to low sea surface temperatures and enhanced upwelling shown by dinoflagellate cysts. Occurrence of Restionaceae in the pollen record suggests northward movement of the winter-rain regime that influenced the study area during the last glacial maximum. Decline of Asteroideae, Restionaceae, and Ericaceae in the pollen record shows that temperate vegetation migrated out of the study area about 17,500 cal yr B.P., probably because of warming during the last deglaciation. The warming in southwestern Africa was associated with weakened upwelling and increased sea surface temperatures, 2000–2800 years earlier than in the Northern Hemisphere. Aridification 14,300–12,600 cal yr B.P. is characterized by a prominent increase of desert and semi-desert pollen without the return of temperate vegetation. This aridification corresponds to enhanced upwelling off Namibia and cooler temperatures in Antarctica, and it might have been influenced by oceanic thermohaline circulation. Aridification 11,000–8900 cal yr B.P. is out of phase with the northern African climate. Reduction of the water vapor supply in southwestern Africa at that time may be related to northward excursions of the Intertropical Convergence Zone.
Middle Pleistocene Climate Change Recorded in Fossil Mammal Teeth from Tarija, Bolivia, and Upper Limit of the Ensenadan Land-Mammal Age
Authors: MacFadden Bruce J.
Published: September 2002

Fossiliferous middle Pleistocene sediments of the Tarija basin of southern Bolivia contain a classic Ensenadan land-mammal fauna. New carbon isotopic data reported here for 50 specimens of the grazing mammals Equus (horse) and Cuvieronius (mastodon), documented from eight stratigraphic levels at Tarija, vary significantly in the δ13C values of their teeth. The pattern of variation appears to reflect the proportion of C3 and C4 grasses eaten during colder (more C3) and warmer (more C4) times. Within age limits set by associated magnetostratigraphy, the cold periods can be correlated with particular even-numbered stages in the marine oxygen-isotope record, and the warm periods can be correlated with odd-numbered stages. The oldest fossil teeth analyzed from the Tarija section can thereby be assigned to stage 29, and the youngest to stages 17 or 15, that is; the teeth range in age from about 1.1 myr to as young as 0.7 myr. Based on correlation of the upper part of the Tarija beds to the isotopic stages, the upper limit of the Ensenadan land-mammal age is between 0.7 and 0.6 myr, which is younger than stated in most previous studies.
Stratigraphic Evidence for the Uplift of the Tibetan Plateau between ∼1.1 and ∼0.9 myr Ago
Authors: Sun Jimin , Liu Tungsheng
Published: September 2002

Uplift of the Tibetan Plateau is manifest not only in widespread denudation, but also by an increased deposition rate of sediment, near or far from the exhumed regions. Our results indicate that the mass accumulation rate (MAR) of eolian dust increased between ∼1.1 and ∼0.9 myr ago. We associate this increase in MAR and median grain size with uplift of the Tibetan Plateau and its adjacent regions during this period. This Middle Pleistocene uplift can also be evidenced by the age of volcanism in the marginal region, the existence of thick conglomerate deposits surrounding the uplifted plateau, and the increased sedimentation rate of lacustrine deposits in the Qaidam Basin (northeastern Tibetan Plateau) between ∼1.1 and ∼0.9 myr ago. The correlation between the loess and marine records indicates that after ∼0.9 myr ago, these two records correlate well. This good correlation probably suggest that the Middle Pleistocene upheaval event not only brought the plateau into the cryosphere, but also enhanced the coupling of regional-scale Chinese loess transportation and deposition to the global ice volume variations through its effects on glacial grinding, rock denudation, and east Asian monsoonal circulation.
Impacts and Timing of the First Human Settlement on Vegetation of the Faroe Islands
Authors: Hannon Gina E. , Bradshaw Richard H. W.
Published: September 2002

Stratigraphically precise AMS-radiocarbon-dated plant remains, pollen, charcoal, and microtephra analyses from the Faroe Islands were used to establish the timing and effects of the first human settlement. The first occurrence of cultivated crops from three locations dated from as early as the sixth century A.D. and was older than implied from previous archaeological and historical studies, but consistent with earlier palaeoecological investigations. The effects of settlement on the vegetation were rapid and widespread. The transformation of the flora of this fragile ecosystem was best expressed by the large assemblage of ruderal, postsettlement plants recorded as macrofossils. The earliest known introduction of domestic animals (sheep/goat) was ca. A.D. 700. Their arrival on these relatively small islands probably contributed to the widespread change in vegetation and the loss of restricted native woody cover. Settlement was the critical disturbance that transformed an ecosystem that was already stressed by climatic change, as sensed by regional marine sediments. The settlement dates conform to a pattern of older dates developing from throughout the north Atlantic region.
European Climatic Response to Millennial-Scale Changes in the Atmosphere–Ocean System during the Last Glacial Period
Authors: Goñi Marı́a Fernanda Sánchez , Turon Jean-Louis , Eynaud Frédérique , Gendreau Sandra
Published: September 2002

Pollen, foraminifer, dinocyst, and coarse lithic high-resolution analyses and δ18O measurements have been carried out for the last-glacial section of marine core MD95-2042 located near the southwestern margin of the Iberian Peninsula. The pollen data indicate a high frequency of vegetational changes on the adjacent continent during this period, suggesting a climatic variability very similar to that of the Dansgaard-Oeschger cycles recorded by the Greenland ice cores. The detailed direct correlation of the terrestrial and marine proxy data from core MD95-2042 indicates a three-phase pattern of Heinrich events in land and ocean environments. The first and last phases of the H5 and H4 events are characterized by a mild and humid climate in southwestern Europe, probably associated with the European origin of the ice-rafted detritus. The middle phase exhibits a cold and dry climate in Iberia linked with the maximum input of ice-rafted detritus. This phase seems to correspond with the Laurentide ice-sheet surges. Between the Heinrich events, several cold and dry periods on land are correlated with stades of the Dansgaard-Oeschger cycles. The impact of the Dansgaard-Oeschger stades in southwestern Europe seems to be preferentially connected to the cold winter air masses reaching this mid-latitude region.
Rapid Ice Margin Fluctuations during the Younger Dryas in the Tropical Andes
Authors: Rodbell Donald T. , Seltzer Geoffrey O.
Published: September 2002

Radiocarbon dated lacustrine sequences in Perú show that the chronology of glaciation during the late glacial in the tropical Andes was significantly out-of-phase with the record of climate change in the North Atlantic region. Fluvial incision of glacial-lake deposits in the Cordillera Blanca, central Perú, has exposed a glacial outwash gravel; radiocarbon dates from peat stratigraphically bounding the gravel imply that a glacier advance culminated between ∼11,280 and 10,990 14C yr B.P.; rapid ice recession followed. Similarly, in southern Perú, ice readvanced between ∼11,500 and 10,900 14C yr B.P. as shown by a basal radiocarbon date of ∼10,870 14C yr B.P. from a lake within 1 km of the Quelccaya Ice Cap. By 10,900 14C yr B.P. the ice front had retreated to nearly within its modern limits. Thus, glaciers in central and southern Perú advanced and retreated in near lockstep with one another. The Younger Dryas in the Peruvian Andes was apparently marked by retreating ice fronts in spite of the cool conditions that are inferred from the ∂18O record of Sajama ice. This retreat was apparently driven by reduced precipitation, which is consistent with interpretations of other paleoclimatic indicators from the region and which may have been a nonlinear response to steadily decreasing summer insolation.
Tree-Ring Dating of Extreme Lake Levels at the Subarctic–Boreal Interface
Authors: Bégin Yves
Published: September 2002

The dates of extreme water levels of two large lakes in northern Quebec have been recorded over the last century by ice scars on shoreline trees and sequences of reaction wood in shore trees tilted by wave erosion. Ice-scar chronologies indicate high water levels in spring, whereas tree-tilting by waves is caused by summer high waters. A major increase in both the amplitude and frequency of ice floods occurred in the 1930s. No such change was indicated by the tree-tilting chronologies, but wave erosion occurred in exceptionally rainy years. According to the modern record, spring lake-level rise is due to increased snowfalls since the 1930s. However, the absence of erosional marks in a large number of years since 1930 suggests a high frequency of low-water-level years resulting from dry conditions. Intercalary years with very large numbers of marked trees (e.g., 1935) indicate that the interannual range of summer lake levels has increased since the 1930s. Increased lake-flood frequency is postulated to be related to a slower expansion of arctic anticyclones, favoring the passage of cyclonic air masses over the area and resulting in abundant snowfall in early winter. Conditions in summer are due to the rate of weakening of the anticyclones controlling the position of the arctic front in summer. This position influences the path of the cyclonic air masses, which control summer precipitation and consequently, summer lake levels in the area.
Far-Field Test of the ICE-4G Model of Global Isostatic Response to Deglaciation Using Empirical and Theoretical Holocene Sea-Level Reconstructions for the Fiji Islands, Southwestern Pacific
Authors: Nunn Patrick D. , Peltier W. Richard
Published: September 2002

Holocene paleosea-level data for Fiji, represented by 77 dates and emergence magnitudes, are presented, screened, and adjusted. Most data are from coral microatolls, potentially the most precise paleosea-level indicators in this region. Holocene sea-level changes are reconstructed for five areas within Fiji known to have had different late Quaternary tectonic histories. Resulting analysis suggests that postglacial sea level in Fiji reached its present level more than 6900 14C yr B.P. It also suggests either that a single maximum 5650–3200 14C yr B.P. (perhaps +2.19 m but more likely +1.35–1.50 m) occurred or that two maxima occurred 6100–4550 14C yr B.P. (+0.75–1.85 m) and 3590–2800 14C yr B.P. (+0.90–2.46 m). Broad agreement exists between these empirical sea-level reconstructions and those derived theoretically using the ICE-4G model (predicted maximum ∼4000 14C yr B.P.; ∼+2.1 m). This suggests that both methods of reconstructing Holocene sea-level changes are valid, as are the assumptions underpinning the ICE-4G model. The most important of these, that eustatic sea level had effectively stopped rising by late middle-Holocene time (5000–4000 yr B.P.), is confirmed by observations from Fiji.
Implications for Late Pleistocene Mastodon Diet from Opal Phytoliths in Tooth Calculus
Authors: Gobetz Katrina E. , Bozarth Steven R.
Published: September 2002

Calculus removed from the molar teeth of four American mastodons (Mammut americanum) contained opal phytoliths which reflect major dietary components. Three samples contained abundant grass phytoliths (ca. 86% of total), with long cells and trapezoidal pooid short cells dominant (ca. 25 and 31%, respectively). Dicot phytoliths from hackberry (Celtissp.) seeds and indeterminate deciduous trees were rare (1–3%), though well preserved, whereas phytoliths from conifer trees were not recognizable in any of the samples. Comparative analysis of calculus from modern and fossil browsers and mixed feeders implies that dicots and conifers are nearly invisible in the phytolith record. This scarcity may result from poor preservation, low silica production in woody taxa, and/or animals' selection of young, silica-poor leaves and shoots. However, abundant grass phytoliths in the mixed feeders suggest that presence versus absence of grass phytoliths may distinguish mixed feeders and grazers from browsers. Mastodons are traditionally considered browsers, but grass phytolith assemblages in three individual mastodons contained similarly high concentrations of pooids, suggesting that these grasses were a significant part of the diet. Abundant pooid phytoliths, in addition to diatoms, indicate that these mastodons grazed in a cool, moist late Pleistocene environment, possibly near water.
Ecosystem Impact of the Campanian Ignimbrite Eruption in Late Pleistocene Europe
Authors: Fedele Francesco G. , Giaccio Biagio , Isaia Roberto , Orsi Giovanni
Published: September 2002

The dating of the Campanian Ignimbrite (CI) eruption to ∼37,000 cal yr B.P. draws attention to the coincidence of this volcanic catastrophe and the suite of coeval, Late Pleistocene biocultural changes that occurred within and outside the Mediterranean region. These included the Middle to Upper Paleolithic cultural transition and the supposed change from Neanderthal to “modern” Homo sapiens anatomy, a subject of sustained debate. No less than 150 km3 of magma were extruded in the CI eruption, the signal of which can be detected in Greenland ice cores. As widespread discontinuities in archaeological sequences are observed at or following the CI event, a significant interference with ongoing human processes in Mediterranean Europe is hypothesized.
Changes in the Thermal Climate in Northwestern Europe during Marine Oxygen Isotope Stage 3, Estimated from Fossil Insect assemblages
Authors: Coope G. Russell
Published: September 2002

More than 30 fossil coleopteran (beetle) assemblages have been recorded from oxygen isotope stage 3 in northern Europe, comprising several hundred identified species. Using the mutual climatic range method for quantifying palaeotemperatures, these assemblages show that the climates of the times can be divided into two distinct interstadial types. One, a short phase of temperate/oceanic climate occurred between 43,000 and 42,000 14C yr B.P. when conditions were not much different from those of the present day. In spite of the temperate climate, trees did not colonize northwestern Europe at this time. Two, both before and after this temperate interlude there were phases of cold/continental climate during which summers were too cold for trees to grow and winters were of Siberian intensity. It is possible that periods of even colder conditions intervened from time to time between the interstadial but, because of the intensity of the cold, biological systems were so inhibited that no fossil evidence for them can be found in northern Europe. Evidence for them must be sought in the fossil records from the warmer parts of southern Europe or in the physical evidence in the Greenland ice cores.
Pharmacological characterization of a novel cell line expressing human α4β3δ GABAA receptors
Authors: Brown N , Kerby J , Bonnert T P , Whiting P J , Wafford K A
Published: September 2002

The pharmacology of the stable cell line expressing human α4β3δ GABAA receptor was investigated using whole‐cell patch‐clamp techniques.

α4β3δ receptors exhibited increased sensitivity to GABA when compared to α4β3γ2 receptors, with EC50's of 0.50 (0.46, 0.53) μM and 2.6 (2.5, 2.6) μM respectively. Additionally, the GABA partial agonists piperidine‐4‐sulphonate (P4S) and 4,5,6,7‐tetrahydroisothiazolo‐[5,4‐c]pyridin‐3‐ol (THIP) displayed markedly higher efficacy at α4β3δ receptors, indeed THIP demonstrated greater efficacy than GABA at these receptors.

The δ subunit conferred slow desensitization to GABA, with rate constants of 4.8±0.5 s for α4β3δ and 2.5±0.2 s for α4β3γ2. However, both P4S and THIP demonstrated similar levels of desensitization on both receptor subtypes suggesting this effect is agonist specific.

α4β3δ and α4β3γ2 demonstrated equal sensitivity to inhibition by the cation zinc (2–3 μM IC50). However, α4β3δ receptors demonstrated greater sensitivity to inhibition by lanthanum. The IC50 for GABA antagonists SR‐95531 and picrotoxin, was similar for α4β3δ and α4β3γ2. Likewise, inhibition was observed on both subtypes at high and low pH.

α4β3δ receptors were insensitive to modulation by benzodiazepine ligands. In contrast Ro15‐4513 and bretazenil potentiated GABA responses on α4β3γ2 cells, and the inverse agonist DMCM showed allosteric inhibition of α4β3γ2 receptors.

The efficacy of neurosteroids at α4β3δ receptors was greatly enhanced over that observed at α4β3γ2 receptors. The greatest effect was observed using THDOC with 524±71.6% potentiation at α4β3δ and 297.9±49.7% at α4β3γ2 receptors. Inhibition by the steroid pregnenolone sulphate however, showed no subtype selectivity. The efficacy of both pentobarbitone and propofol was slightly augmented and etomidate greatly enhanced at α4β3δ receptors versus α4β3γ2 receptors.

We show that the α4β3δ receptor has a distinct pharmacology and kinetic profile. With its restricted distribution within the brain and unique pharmacology this receptor may play an important role in the action of neurosteroids and anaesthetics.

British Journal of Pharmacology (2002) 136, 965–974. doi:10.1038/sj.bjp.0704795
Two tyrosine residues in the first transmembrane helix of the human vasoactive intestinal peptide receptors play a role in supporting the active conformation
Authors: Perret J , Vertongen P , Solano R M , Langer I , Cnudde J , Robberecht P , Waelbroeck M
Published: September 2002

We investigated the human vasoactive intestinal polypeptide (VIP) receptors VPAC1 and VPAC2 mutated at conserved tyrosine residues in the first transmembrane helix (VPAC1 receptor Y146A and Y150A and VPAC2 receptor Y130A and Y134A).

[125I]‐Acetyl‐His1 [D‐Phe2, K15, R16, L27]‐VIP (1–7)/GRF (8–27) (referred to as [125I]‐VPAC1 antagonist) labelled VPAC1 binding sites, that displayed high and low affinities for VIP (IC50 values and per cent of high affinity binding sites: wild‐type, 1 nM (57±9%) and 160 nM; Y146A, 30 nM (40±8%) and 800 nM; Y150A, 4 nM (27±8%) and 300 nM). [R16]‐VIP behaved as a ‘super agonist’ at both mutated VPAC1 receptors and the efficacies of VIP analogues modified in positions 1, 3 and 6 were significantly decreased.

VIP was less potent at the Y130A and Y134A mutated VPAC2 receptors (EC50 200 and 400 nM, respectively) than at the wild‐type VPAC2 receptor (EC50 7 nM). Furthermore, [hexanoyl‐His1]‐VIP behaved as a ‘super agonist’ at the two mutated VPAC2 receptors, and VIP analogues modified in positions 1, 3 and 6 were less potent and efficient at the mutated than at wild‐type VPAC2 receptors. However, the Y130A and Y134A mutants could not be studied in binding assays

Our results suggest that the conserved tyrosine residues do not interact directly with the VIP His1, Asp3 or Phe6 residues (that are necessary for receptor activation), but stabilize the correct active receptor conformation.

British Journal of Pharmacology (2002) 136, 1042–1048. doi:10.1038/sj.bjp.0704802
Distinct roles of GPVI and integrin α2β1 in platelet shape change and aggregation induced by different collagens
Authors: Jarvis Gavin E , Atkinson Ben T , Snell Daniel C , Watson Steve P
Published: September 2002

Various platelet membrane glycoproteins have been proposed as receptors for collagen, in some cases as receptors for specific collagen types. In this study we have compared the ability of a range of collagen types to activate platelets.

Bovine collagen types I–V, native equine tendon collagen fibrils and collagen‐related peptide (CRP) all induced platelet aggregation and shape change.

Responses were abolished in FcRγ chain‐deficient platelets, which also lack GPVI, indicating a critical dependence on the GPVI/FcRγ chain complex.

Responses to all collagens were unaffected in CD36‐deficient platelets.

A monoclonal antibody (6F1) which binds to the α2 integrin subunit of human platelets had a minimal effect on the rate and extent of aggregation induced by the collagens; however, it delayed the onset of aggregation following addition of all collagens. For shape change, 6F1 abolished the response induced by collagen types I and IV, substantially attenuated that to collagen types II, III and V, but only partially inhibited Horm collagen.

Simultaneous blockade of the P2Y1 and P2Y12 receptors, and inhibition of cyclo‐oxygenase demonstrated that CRP can activate platelets independently of ADP and TxA2; however, responses to the collagens were dependent on these mediators.

This study confirms the importance of the GPVI/FcRγ chain complex in platelet responses induced by a range of collagen agonists, while providing no evidence for collagen type‐specific receptors. It also provides evidence for a modulatory role of α2β1, the significance of which depends on the collagen preparation.

British Journal of Pharmacology (2002) 137, 107–117. doi:10.1038/sj.bjp.0704834
Endothelial nitric oxide modulates perivascular sensory neurotransmission in the rat isolated mesenteric arterial bed
Authors: Ralevic Vera
Published: September 2002

A possible role of nitric oxide (NO) as a modulator of capsaicin‐sensitive sensory neurotransmission in blood vessels was investigated in the rat isolated mesenteric arterial bed.

Electrical field stimulation (EFS) of methoxamine‐preconstricted mesenteric beds elicited frequency‐dependent vasorelaxation mediated by capsaicin‐sensitive sensory nerves. NG‐nitro‐L‐arginine methyl ester (L‐NAME, 10 and 300 μM) and 7‐nitroindazole (7‐NI, 100 μM), inhibitors of nitric oxide synthase (NOS), augmented sensory neurogenic vasorelaxation. D‐NAME (300 μM), 6‐aminoindazole (100 μM) and Nω‐propyl‐L‐arginine (50 nM), a selective inhibitor of neuronal NOS, were without effect. The effect of 10 μM L‐NAME was reversed by L‐arginine (1 mM), the substrate for NOS.

L‐NAME (300 μM) and 7‐NI (100 μM) had no significant effect on vasorelaxations to calcitonin gene‐related peptide (CGRP), the principal motor neurotransmitter of capsaicin‐sensitive sensory nerves in rat mesenteric arteries, or to capsaicin, indicating a prejunctional action. The inhibitors of NOS had no effect on vasorelaxation to forskolin, but augmented vasorelaxation to sodium nitroprusside (SNP).

Removal of the endothelium augmented sensory neurogenic vasorelaxation, but did not affect vasorelaxation to CGRP, indicating a prejunctional action of endothelial NO.

In the absence of endothelium, L‐NAME (300 μM) inhibited, and 7‐NI (100 μM) caused no further augmentation of sensory neurotransmission.

SNP (100 nM), a nitric oxide donor, attenuated sensory neurogenic relaxations to EFS.

In rat isolated thoracic aortic rings, L‐NAME (100 μM) and 7‐NI (100 μM) attenuated concentration‐dependent relaxations to acetylcholine.

These data show that NO modulates sensory neurotransmission evoked by EFS of the rat isolated mesenteric arterial bed, and that when NO synthesis is blocked sensory neurogenic relaxation is augmented. The source of NO is the vascular endothelium.

British Journal of Pharmacology (2002) 137, 19–28. doi:10.1038/sj.bjp.0704837
Immune reconstitution after haematopoietic cell transplantation in children: immunophenotype analysis with regard to factors affecting the speed of recovery
Authors: Kalwak Krzysztof , Gorczyńska Ewa , Toporski Jacek , Turkiewicz Dominik , Slociak Malgorzata , Ussowicz Marek , Latos‐Grażyńska Elżbieta , Król Marzena , Boguslawska‐Jaworska Janina , Chybicka Alicja
Published: September 2002

Summary.  Immune reconstitution was studied prospectively in 66 children who underwent 77 haematopoietic cell transplantations (HCT): 46 autologous HCTs in 39 patients and 31 allogeneic HCTs in 27 patients. We studied the dynamic analysis of immune recovery with regard to potential factors affecting its speed, including age, type of HCT, diagnosis, graft‐versus‐host disease (GvHD) and cytomegalovirus (CMV) infection reactivation. Absolute counts of different lymphocyte subsets and immunoglobulin serum levels were determined in peripheral blood of patients on d −7 and +16, and then at various intervals up to 24 months post transplant. Common patterns of immune recovery after both allogeneic and autologous HCT were identified: (i) CD4+CD45RO+ peripheral T‐cell expansion on d +16; (ii) inverted CD4+:CD8+ ratio from d +30 onwards; (iii) rapid natural killer (NK) cell (CD16±CD56+) count normalization. We observed prolonged T‐cell lymphopenia (CD3+, CD3+CD4+, CD4+CD45RA+) until 24 months after autologous HCT, whereas in the allogeneic setting CD3+CD4+ cells, including naive CD45RA+ cells, returned to normal values at 9 months post transplant. Age > 10 years and coexistence of GvHD and CMV reactivation were associated with a substantial delay in T‐ (CD4+, including CD45RA+) and B‐cell recovery after allogeneic HCT. Multidrug GvHD prophylaxis resulted in impaired T‐ (CD4+, CD4+CD45RA+) and B‐cell reconstitution only in the early phase after allogeneic HCT (up to 4 months). Our results demonstrated that T‐cell recovery was severely impaired in children after autologous HCT. It should be emphasized that specific approaches to enhance immune reconstitution are necessary to control minimal residual disease and avoid the risk of infectious complications in the autologous setting. Thymic involution after allogeneic HCT seems to be associated with age and coexistence of GvHD and CMV reactivation.
Continuous complete clinical and molecular remission in two patients with refractory lymphoid malignancies after autografting followed by allogeneic stem cell transplantation with reduced intensity conditioning
Authors: Mitterbauer Margit , Kalhs Peter , Keil Felix , Prinz Erika , Moser Karin , Mannhalter Christine , Mitterbauer Gerlinde , Brugger Stefan , Gisslinger Heinz , Lechner Klaus , Greinix Hildegard T.
Published: September 2002

Summary. We present a 60‐year‐old patient with primary refractory non‐Hodgkin's lymphoma and a 58‐year‐old patient with multiple myeloma with relapse after first autologous stem cell transplantation (ASCT), who underwent ASCT followed by allogeneic stem cell transplantation (alloSCT) with reduced intensity conditioning consisting of fludarabine and a single dose of total body irradiation. For graft‐versus‐host disease prophylaxis cyclosporine and mycophenolate mofetyl were given. Complete donor chimaerism was observed on d 28 after SCT. Both patients achieved sustained complete haematological and molecular remission of the immunoglobulin kappa light chain (Igκ) rearrangement and are alive and well 17 and 16 months after SCT respectively.
Factors predictive of early death in patients receiving high‐dose CHOP (ACVB regimen) for aggressive non‐Hodgkin's lymphoma: a GELA study
Authors: Dumontet Charles , Mounier Nicolas , Munck Jean Nicolas , Bosly André , Morschauser Frank , Simon Daniele , Marit Gérald , Casasnovas Olivier , Reman Oumédaly , Molina Thierry , Reyes Felix , Coiffier Bertrand
Published: September 2002

Summary. Death during the induction phase of chemotherapy remains a common event in patients with aggressive non‐Hodgkin's lymphoma (NHL). In a series of patients with aggressive NHL homogeneously treated with intensive induction chemotherapy [ACVB (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) regimen], we determined the clinical and biological parameters that were predictive of early death. Early death was defined as death, for whatever reason, occurring within 100 d of randomization. Predictive factors were identified by logistic regression and an index predictive for individual risk of early death was designed. Among the 2210 patients treated with ACVB, there were 162 (7·3%) early deaths. There was no significant reduction in the rate of early death between 1987 and 1998. In a multivariate analysis, age > 60 years, Eastern Cooperative Oncology Group performance status > 1, serum lactate dehydrogenase > normal, serum albumin < 30 g/l, leucocyte counts > 10 × 109/l and haemoglobin levels < 8·5 g/dl were found to be independent predictive factors for early death. An early death index was designed, enabling the evaluation of the individual risk of early death in young (range 2–31% risk of early death) and elderly patients (range 5–53%). Clinical and biological parameters available at diagnosis can help physicians identify patients with aggressive lymphoma at low or high risk of early death.
Clinical and biological effects of treatment with amifostine in myelodysplastic syndromes
Authors: Invernizzi Rosangela , Pecci Alessandro , Travaglino Erica , Gobbi Paolo G. , Malabarba Lucia , Ramajoli Isabella , Ascari Edoardo
Published: September 2002

Summary. We treated six patients with primary myelodysplastic syndrome (MDS) with amifostine (200 mg/m2 i.v./three times a week for three consecutive weeks). Neutrophil counts were more frequently increased than platelet and reticulocyte counts, but no reduction of the transfusion requirement was observed. Significant reduction of the marrow blasts was observed in one case of refractory anaemia with excess of blasts. In vitro stimulation of haematopoiesis was observed in five cases. The apoptotic rate of marrow cells was significantly diminished even after the first course. Our findings show fairly good clinical and biological response to amifostine in MDS.
Trends in the prey size‐based trophic niches of feral and House Cats Felis catus L.
Authors: Pearre  , Maass
Published: September 2002

House Cats Felis catus L., whether attached to human households or not, appear to be versatile opportunistic predators. Their principal prey in most areas are mammals (rodents and rabbits), with bird prey secondary. Trophic niche breadth, as measured by the standard deviation of the spectrum of logarithmically transformed prey sizes (‘SLH’), shows a latitudinal trend, being greater in low latitudes: it is also greater in periods of high prey availability. This appears to be influenced by inclusion of very small prey, especially insects, in areas and seasons when they are available. Both the niche breadth and the mean prey size (niche position) appear to be constant as population mean cat size increases. The most common prey size for cats is about 1% of their own body weights, which is much less than most previously reported values for carnivores.
Risk of congenital inguinal hernia in siblings: a record linkage study
Authors: Jones Michael E. , Swerdlow Anthony J. , Griffith Myfanwy , Goldacre Michael J.
Published: September 2002

Using data from the Oxford Record Linkage Study (ORLS), we conducted a case‐control study to estimate the sex‐specific risks of inguinal hernia in siblings of children with this condition. There were 1921 male and 347 female cases born during 1970–86 who were operated on for inguinal hernia at ages 0–5 years during 1970–87, with 12 886 male and 2534 female control subjects. The relative risk of inguinal hernia was 5.8 [95% confidence interval 4.0–8.4] for brothers of male cases and 4.3 [2.1–8.7] for brothers of female cases (both relative to brothers of control subjects). The relative risk was 3.7 [1.8–7.9] for sisters of male cases and 17.8 [6.9–46.3] for sisters of female cases (both relative to sisters of control subjects). The pattern of sex‐dependent risks, particularly the large risk for sisters of female cases, suggests a multifactorial threshold model for the disease. Girls have much lower rates of inguinal hernia than boys, and if these rates are low because of a low susceptibility to disease due to the absence of a sex‐related risk factor, then those girls who develop disease might have a potentially large contribution to susceptibility from genetic or intrauterine risk factors unrelated to sex.
The Treatment of Lead‐exposed Children (TLC) trial: design and recruitment for a study of the effect of oral chelation on growth and development in toddlers
Authors: Treatment of Lead‐exposed Children Trial Group
Published: September 2002

Exposure to lead impairs cognitive development in young children, but the benefits of lowering blood lead pharmacologically are not clear. This report describes the design, recruitment, enrolment and baseline results of the Treatment of Lead‐Exposed Children (TLC) trial, a randomised, multicentre, placebo‐controlled, double‐blind clinical trial of the effects of treating lead‐exposed children with succimer, a drug that enhances urinary excretion of lead, on cognitive, behavioural and physical development. TLC clinical sites were in Baltimore, Cincinnati and Columbus, Newark and Philadelphia. Children were eligible for TLC if they were between 12 and 33 months of age, had a confirmed blood lead concentration between 20 and 44 μg/dL and lived in a residence suitable for lead dust reduction. Randomised children received up to three 26‐day courses of succimer or placebo, and were then followed for 3 years. The study can detect a three‐point difference in full‐scale IQ at 3‐year follow‐up. Statistical power for the other end points is more difficult to estimate. A total of 1854 children were evaluated and 780 children were randomised between August 1994 and January 1997. The mean age of randomised children was 24 months and mean blood lead level 26 μg/dL. Three‐quarters were African–American. Most children had poor, single mothers who had completed 12 or fewer years of school and who lived in older, poorly maintained residences.
Effect of epidermal growth factor on cell proliferation in normal and wounded connective tissue
Authors: Malcherek Per , Schultz Gregory , Wingren Urban , Franzén Lennart
Published: September 2002

Epidermal growth factor has been previously shown to stimulate connective tissue repair in the perforated rat mesentery. The mechanism by which epidermal growth factor accelerates closure of mesenteric perforations has not been established, but epidermal growth factor may stimulate mitosis, contraction, migration, or angiogenesis. In the present investigation, the effect of epidermal growth factor on connective tissue cell proliferation was studied during the initial phase of repair of mesenteric perforations and in unwounded mesentery. Laparotomies were performed on Sprague‐Dawley rats, and standardized perforations were made with a scalpel in the center of the mesenteric “windows,” leaving every second window as an internal control. Twice daily for 4 consecutive days, beginning on the day of surgery, the animals received by intraperitoneal injection either 10 µg of epidermal growth factor dissolved in phosphate‐buffered saline solution or phosphate‐buffered saline solution alone. Cell proliferation was measured by either mitotic index of fibroblasts and mesothelial cells or DNA content of individual fibroblast cell nuclei in the wound area or in unperforated control windows. Laparotomy alone was found to enhance proliferation during the early postoperative period, as shown by increased numbers of S + G2 fibroblasts and a greater mitotic index. Epidermal growth factor treatment increased the mitotic index in perforated windows on the third postoperative day, compared with controls treated with phosphate‐buffered saline solution, but did not significantly increase either the number of S + G2 fibroblasts or the mitotic index in unwounded tissue. Also, the proliferative response after epidermal growth factor treatment was significantly higher in wounded tissue. This study shows that epidermal growth factor stimulates proliferation of connective tissue cells in wounded but not unwounded tissue, and such enhancement of fibroblast proliferation might be of importance in epidermal growth factor—stimulated connective tissue repair.
Epidermal growth factor promotes wound repair of human respiratory epithelium
Authors: Zahm Jean‐Marie , Pierrot Denis , Puchelle Edith
Published: September 2002

Reepithelialization of the airway mucosa is an essential step toward restoring a normal functional protective barrier during the repair of airway epithelial wounds. We investigated the role of epidermal growth factor in the wound healing of human surface epithelial cells cultured from nasal polyp explants on a type I collagen gel in serum‐free defined medium. By using image analysis techniques, we measured the outgrowth area, the ciliated surface, the ciliary beating frequency, and the in vitro wound repair rate in the presence of different epidermal growth factor concentrations. We observed a significant dose‐dependent increase in the outgrowth area (10‐fold increase with epidermal growth factor doses of 0 to 20 ng/ml), in the percentage of the outgrowth surface covered by ciliated cells (30% without epidermal growth factor and 43% with epidermal growth factor 20 ng/ml) and in the ciliary beating frequency (12.6 to 14.5 Hz). The wound repair rate was improved by 29% in the presence of epidermal growth factor 10 ng/ml. These results suggest that epidermal growth factor could be involved in the wound repair process of the airway epithelium.
Mild hypothermia during halothane‐induced anesthesia decreases resistance to Staphylococcus aureus dermal infection in guinea pigs
Authors: Sheffield Clark W. , Sessler Daniel I. , Hunt Thomas K. , Scheuenstuhl Heinz
Published: September 2002

Because various immune functions are impaired at temperatures only 1° to 3° C less than normal, we tested the hypothesis that mild hypothermia during anesthesia impairs resistance to dermal infections. Guinea pigs were anesthetized for 6 hours with 1% inspired halothane. Their core temperatures were maintained at either 39° C (normal for guinea pigs, n = 12) or 36° C (n = 12). Two hours after induction of anesthesia, three doses each of Staphylococcus aureus (108, 107, and 106 organisms) were injected intradermally at nine sites on each animal's back. Core temperatures were not controlled after recovery from the anesthetic, and animals in each group were maintained in the same environment. Four days after anesthesia, each injection site was excised to obtain a count of viable bacteria. Subcutaneous oxygen partial pressure values, averaged over time, were 53 ± 3 mm Hg (mean ± SEM) in the hypothermic group and 62 ± 4 mm Hg in the normothermic group (p = 0.06). Capillary perfusion, as assessed by laser Doppler flowmetry, was comparable in the two groups. One day after injection of 108 bacteria, the area of induration was 89 ± 11 mm2 in the hypothermic group but only 61 ± 6 mm2 in the normothermic group (p < 0.05). On postanesthetic day 4, the area of induration was 72 ± 6 and 59 ± 6 mm2 in the hypothermic and normothermic groups, respectively (p > 0.05). After inoculation with 108 bacteria, the fraction recovered was 1.0 ± 0.2 in the hypothermic groups and 0.6 ± 0.2 in the normothermic group (p < 0.05). After inoculation with 107 and 106 bacteria, the fraction recovered was less than 0.2, and no difference was found between the hypothermic and normothermic animals. Thus mild hypothermia during halothane‐induced anesthesia slightly impairs resistance to dermal infection.
Role of fibrinolysis in the formation of postoperative adhesions
Authors: Holmdahl Lena E. , Al‐Jabreen Mohammed , Risberg Bo
Published: September 2002

It has been hypothesized that peritoneal hypofibrinolysis is of importance in the formation of postoperative adhesions, but results from experiments with fibrinolytic modulators are conflicting. We tested this hypothesis in a controlled prospective study in rabbits, comparing the effects of fibrinolytic inhibition (tranexamic acid) to fibrinolysis enhancement by local instillation of gel containing tissue‐type plasminogen activator. Adhesion formation was measured after 1 week in a strictly standardized way and is presented as a percentage of an induced lesion that was covered by adhesions. Fibrinolytic inhibition significantly increased adhesion formation, both to the parietal peritoneum (34.2%± 3.2%) compared with untreated control (19.7%± 3.3%, p < 0.01) and to the bowel (76.3%± 5.8%) compared with untreated control (51.2%± 8.7%, p < 0.05). Control gel significantly increased adhesions to the parietal peritoneum (35.6%± 4.6%) versus untreated control (19.7%± 3.3%, p < 0.05), whereas gel containing tissue‐type plasminogen activator significantly reduced the amount of adhesions to the parietal peritoneum (4.9%± 1.7%) compared with untreated control (19.7%± 3.3%, p < 0.01) and abolished adhesion formation to the injured bowel. The fibrinolytic system thus seems to be intimately involved in the early formation of intraabdominal adhesions.
Specific effects of glycosaminoglycans in an analog of extracellular matrix that delays wound contraction and induces regeneration
Authors: Shafritz T. Alex , Rosenberg Lawrence C. , Yannas Ioannis V.
Published: September 2002

Previous studies have shown that a simple analog of extracellular matrix delays wound contraction and, if seeded with keratinocytes, inhibits scar synthesis by inducing partial regeneration of the dermis and the epidermis in full‐thickness skin wounds in the guinea pig. The active extracellular matrix analog was selected from a large number of copolymers of type I collagen and chondroitin‐6‐sulfate differing in average pore diameter and degradation rate. However, these previous studies did not provide information on the potential role of the glycosaminoglycan component of this collagen‐glycosaminoglycan matrix. The present study focuses on the effect of substitution of chondroitin‐6‐sulfate by other glycosaminoglycans or with the corresponding proteoglycans. The three substituents of chondroitin‐6‐sulfate studied were dermatan sulfate, decorin (a proteoglycan‐containing dermatan sulfate chain), and aggrecan (a proteoglycan in which 90% of the glycosaminoglycan component was chondroitin‐6‐sulfate). Each test matrix was grafted on full‐thickness skin wounds in the guinea pig, and the wound contraction kinetics were followed. Previous studies have strongly suggested that delay in onset of contraction is necessary for regeneration. Substitution of chondroitin‐6‐sulfate by either dermatan sulfate or decorin increased the delay in wound contraction by the greatest increment. However, the difference between substitution either by the dermatan sulfate chains or by the corresponding proteoglycan was not significant. Substitution of chondroitin‐6‐sulfate by aggrecan did not affect the activity of the extracellular matrix analog. These results suggest that the glycosaminoglycan component of the proteoglycan, rather than the protein core, is responsible for the increment of activity. It is speculated that the morphogenetic activity of the extracellular matrix analog resides in its putative ability to neutralize transforming growth factor‐β, leading thereby to downregulation of the inflammatory response in the wound bed.
Effect of platelet‐derived growth factor on rabbit corneal wound healing
Authors: Stern Michael E. , Waltz Kathleen M. , Beurerman Roger W. , Ghosn Corine R. , Mantras Christine E. , Nicolson Margery , Assouline Michael , Stern Katherine L. , Wheeler Larry A.
Published: September 2002

Human recombinant platelet‐derived growth factor was evaluated with the use of wound healing models in New Zealand albino rabbits. The efficacy of the platelet‐derived growth factor dimers, AA, AB, and BB, was determined in corneal reepithelialization and anterior keratectomy models which examined the healing response in the presence or absence of the basement membrane. All dimers increased the rate of wound healing in both models at 100 µg/ml when compared with control; however, the platelet‐derived growth factor‐BB isoform showed the most dramatic increase in both studies. The strength of the healing stroma after incision was evaluated by means of a tensile strength model. Histologic evaluation of the stromal wound area after 9 days of healing showed a marked increase in the number of keratocytes within the wound bed of the corneas treated with platelet‐derived growth factor‐BB when compared with control corneas. In addition, at 9 days, the epithelial plug was still present in the control corneas but had been extruded to the surface by the granulation tissue in the platelet‐derived growth factor‐BB—treated corneas. These results are indicative of a more advanced stage of healing in treated versus control wounds at 9 days after the operation. A 30% increase in corneal tensile strength versus control was noted after 21 days of healing. Finally, in an in vitro gel contraction assay, platelet‐derived growth factor exhibited a dose‐dependent effect on the contraction of fibroblasts for doses ranging from 0.01 to 10 ng/ml. These results indicate that platelet‐derived growth factor is active in the corneal wound healing process.
Assessment of full‐thickness wounds in the genetically diabetic mouse for suitability as a wound healing model
Authors: Senter Lucy H. , Legrand Edmund K. , Laemmerhirt Karen E. , Kiorpes Timothy C.
Published: September 2002

While using the diabetic C57BL/KsJ db/db mouse as a wound healing model, we encountered several repair patterns which affect its suitability as a predictive screening model for certain indications. For example, wound contraction, albeit impaired, was found to be particularly dependent on bandaging technique and vehicle type. Wounds which had been continuously occluded with Opsite dressings had a high relative variability in contraction, and there was a tendency toward reduced contraction, suggesting that the dressings were acting as a splint. Viscous dosing vehicles inhibited contraction of occluded wounds but appeared to enhance contraction of nonoccluded wounds. In contrast to many other models, occlusion in these studies did not enhance reepithelialization when compared with air exposure (the rate of reepithelialization in db/db mice appeared normal, typically growing 2 mm from each edge in 10 days). Also in contrast to other wound healing models, viscous dosing vehicles when used under occlusion inhibited reepithelialization. However, as seen in other wound healing models, granulation tissue thickness was reliably increased in response to treatment with recombinant human platelet‐derived growth factor‐BB. Our experience with the db/db diabetic mouse model has led us to recommend the use of this animal model only after its limitations have been identified and accepted.