bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the process of growth in cephalopods
Authors: Moltschaniwskyj Natalie A.
Published: June 2004

Many cephalopod species grow throughout their lifetime. Critically, this means that they lack an asymptotic phase of growth, when, for a substantial part of the lifetime, growth slows and body size increases minimally. Understanding the form of the growth curve requires an understanding of the growth processes operating at several biological levels including the relative growth of organs, muscle fibre production and growth, and at the level of proximal composition and protein synthesis. There are key differences in growth processes between fish and cephalopods; cephalopods have a sac-like body form that provides greater surface area for respiration, continuous production of new muscle fibres that ensures a supply of somatic material for growth, and high retention of synthesised protein. These characteristics provide process-orientated explanations for non-asymptotic growth in cephalopods. However, differences found in growth curves of laboratory-reared animals (two-phase growth curve) and of wild animals (single growth curve) suggests that future work will be needed to resolve this paradox. We need to determine the generality of growth processes observed to date, and how biotic and abiotic factors modify these processes during the lifetime of the animals.
The role of hatchling size in generating the intrinsic size-at-age variability of cephalopods: extending the Forsythe Hypothesis
Authors: Pecl G. T. , Steer M. A. , Hodgson K. E.
Published: June 2004

Cephalopods are characterised by extreme variability in size-at-age, with much of this variation attributed to effects of temperature and food. However, even siblings reared under identical conditions display a wide range of sizes after a period of growth. Hatchling size may represent a source of variation encompassed within adult size-at-age data (i) within a given cohort (variation in hatchling size suggests that a cohort’s growth trajectory will have a ‘staggered start’) and (ii) as hatchling size also varies as a function of incubation temperature this will vary across broader scales (i.e. between cohorts). Field-hatchling size data for Sepioteuthis australis were used in simple deterministic simulations, extending Forsythe’s (1993) temperature hypothesis, to investigate the influence of hatchling size on adult size-at-age variability. Within a cohort, our growth projections suggest that after 90 days, a large hatchling growing at a specific constant percentage daily growth rate (%BW day–1), would be approximately double the size of the small hatchling growing at exactly the same rate, irrespective of the growth rate used. When considering growth of different cohorts, decreases in hatchling size, as temperatures increase during a spring/summer spawning season, may be partially counteracting the ‘Forsythe-effect’ of increased growth rate at higher temperatures.
Diversity in growth and longevity in short-lived animals: squid of the suborder Oegopsina
Authors: Arkhipkin Alexander I.
Published: June 2004

This article is an overview of age and growth studies of squid belonging to the suborder Oegopsina, which includes the majority (~215) of squid species inhabiting offshore waters of the continental shelves and pelagic waters of the world ocean. Three main periods in the history of age and growth studies of oegopsin squid are identified. A brief history of the different methods applied to study oegopsin age and growth is presented. The lifespan of oegopsin squid varies from almost 3 months in small pelagic tropical species to 2 years in polar and deepwater species. Generally, the lifespan of similar-sized oegopsin squid increases with latitude. Growth of the majority of oegopsin squid is best described by one of the asymptotic growth functions, but some tropical squid are characterised by non-asymptotic growth. Many aspects of growth variability are discussed, such as ontogenetic, sexual, intra-specific, geographical, inter-annual and inter-specific variations. The fast growth rates of oegopsin squid give them the advantage of passing quickly through the most vulnerable first trophic levels of the oceanic food web, enabling them to compete successfully with nektonic fishes.
Performance of grass and rainforest riparian buffers in the wet tropics, Far North Queensland. 1. Riparian hydrology
Authors: McKergow Lucy A. , Prosser Ian P. , Grayson Rodger B. , Heiner Dale
Published: June 2004

The long and intense storms of the wet tropics present extreme conditions for testing the effectiveness of riparian buffers. This study presents results of a hydrometric investigation of 4 riparian buffers on 2 commercial banana plantations in Far North Queensland, Australia. It investigates runoff generation and riparian hydrology on hillslopes with differing slopes, contributing areas, and topographic convergence. Both grass and rainforest buffers were examined. Surface and subsurface hydrology were measured for 4 wet seasons (December–April) using paired flumes, piezometers, and tensiometers. All buffers experienced large volumes of surface runoff, with peak discharges ranging from 30 L/s on planar hillslopes to 350 L/s on a highly convergent site. Event runoff : rainfall ratios ranged between 0.01 and 0.65. Grass buffers with smaller contributing areas (<0.3 ha) were able to dissipate the energy of surface runoff under all conditions. In a larger (5 ha), highly convergent hillslope, surface runoff became channelised upslope of the buffer and the vetiver hedges and grass were not able to prevent scouring of a channel through the buffer, reducing its performance. Infiltration occurred in all buffers during small events, and at the convergent buffer during large events, most likely due to the presence of deep soil fill. In contrast, exfiltration occurred in the grass buffers on planar and moderately converging slopes during large events. There, the riparian soil approached saturation and return flow and seepage were measured. Under exfiltration, soil strength may be decreased and riparian buffers are needed to decrease erosion hazard. Localised saturation was observed in the rainforest buffer beneath a planar hillslope during large events, where soils were deeper and dried out more quickly than in the adjacent grass buffer. This study documents the high runoff volumes and peak discharges on cropped slopes in the wet tropics, and evaluates riparian hydrological processes. Infiltration is unlikely to be an important buffer function in this environment, but an additional role of buffers is to reduce the erosion hazard presented by exfiltration.
Effect of humic acid, sodium, and calcium additions on the formation of water-stable aggregates in Western Australian wheatbelt soils
Authors: Yamaguchi T. , Takei T. , Yazawa Y. , Wong M. T. F. , Gilkes R. J. , Swift R. S.
Published: June 2004

The effect of humic acids extracted from coal waste and peat on the formation of water-stable aggregates in kaolinitic soils from the wheatbelt of Western Australia and a prepared kaolinite–quartz mix were assessed. This effect was compared with that produced by adding calcium to the soils. In the case of kaolinite–quartz mix, the treated samples were measured for micro-aggregation since macro-aggregates were not formed under the experimental conditions. The wheatbelt soils were already aggregated and the measurement was of the further macro-aggregation of these aggregates. In kaolinite–quartz, calcium additions alone enhanced the formation of stable micro-aggregates. This effect was amplified with additions of humic acids when up to 30% of the clay-sized particles were aggregated into larger aggregates. This humic acid effect was not observed in the sodium dominated mineral system.In contrast to the kaolinite-quartz samples, the selection of wheatbelt soils used in this study responded little to calcium additions alone. Humic acid increased the size of aggregates in the sodium-treated soils presumably due to the presence of aluminium in the system studied at pH 4.5. The aluminium ions can be expected to act as the bridging cations between the negatively charged clay-sized particles and the anionic groups present in the organic matter. The ineffectiveness of calcium in these soils allowed the positive effect of the humic acids to be expressed clearly. These findings provide another management option for improving the soil structure of salt-affected land because some of these soils are unlikely to respond to gypsum application.
The process of sulfide oxidation in some acid sulfate soil materials
Authors: Ward N. J. , Sullivan L. A. , Fyfe D. M. , Bush R.T. , Ferguson A. J. P.
Published: June 2004

The process of sulfide oxidation in acid sulfate soils (ASS) is complex, involving the formation of numerous oxidation products. In this study the sulfide oxidation process was examined in 2 ASS materials over a period of 36 days using laboratory incubation experiments. Both ASS materials experienced substantial sulfide oxidation and acidification during incubation. The oxidation of pyrite was the primary cause of acidification in these ASS materials. Although a decrease in magnetic susceptibility (χ) over the initial 4 days of incubation suggested the rapid oxidation of ferromagnetic iron monosulfide greigite (Fe3S4), the total acid volatile sulfur (SAV) fraction increased in concentration by an order of magnitude over the initial 8 days of incubation. Oxygen (O2) concentration profiles indicated the presence of anoxic conditions in the centre of the incubating materials even after 16 days of exposure to the atmosphere enabling SAV formation to occur. The oxidation of the SAV fraction did not result in substantial acidification. A large proportion of the water-soluble iron released by sulfide oxidation was precipitated as iron oxides and hydroxides. Sulfate (SO42–) was the dominant sulfur species produced from sulfide oxidation in both ASS materials, although water-soluble SO42– was a poor indicator of the extent of sulfide oxidation. The sulfoxyanion intermediates, thiosulfate (S2O32–) and tetrathionate (S4O62–), were detected only in the early stages of incubation, with minimal amounts being detected after the initial 4 days. The relative abundance of these 2 intermediate sulfur species appeared to be dependent on the soil pH, with S4O62– dominating S2O32– in the more acidic ASS material (i.e. pH <6) as has been observed in previous studies. The diminishing presence of sulfoxyanion intermediates as oxidation progressed was indicative that ferric ion (Fe3+) and bacterial catalysis were driving the oxidation processes. While these sulfoxyanion intermediates only constituted a small percentage of the reduced inorganic sulfur (RIS) fraction, they accounted for up to 9.3% of the total soluble sulfur fraction. Elemental sulfur (S0) was not an important sulfide oxidation product in the ASS materials examined in this study.
Chemistry, radiocarbon ages, and development of a subtropical acid peat in Queensland, Australia
Authors: Krull Evelyn S. , Thompson Clifford H. , Skjemstad Jan O.
Published: June 2004

A subtropical peat, developed on a costal plain in southern Queensland, has been studied with respect to its morphology, radiocarbon (14C) age, total organic carbon (C) content, stable C isotopic (δ13C) values, and spectroscopic characteristics (13C-NMR and FTIR). The combination of techniques allowed for an interpretation of changes in peat development over time, an assessment of paleoclimatic changes that apparently occurred during peat growth, and a comparison with perched lake sediments on Fraser Island.Geochemical data from the peat showed a relative increase in abundance of aromatic C (which may include charcoal) from the Pleistocene to the early Holocene and much decreased abundances of aromatic C thereafter. This trend may be due to changes in fire frequency from the Pleistocene–early Holocene (high fire frequency) to the early and middle Holocene (relatively low fire frequency). This interpretation is consistent with other published data from this area, showing increased aridity, increased fire frequency and dominance of sclerophyll forest during the late Pleistocene–early Holocene.Another significant geochemical change in the acid peat occurred within the middle to late Holocene. This period is characterised by highly 13C-depleted organic matter and a comparably high alkyl C (lipid) content. These data are interpreted as indicating wetter and year-round waterlogged conditions, possibly associated with poor drainage during the Holocene sea level maximum c. 5500–3000 years BP. By comparison, abundance of alkyl C decreased and δ13C values increased in the latest Holocene. The geochemical data from the acid peat point to the occurrence of a dry phase during the late Pleistocene to early Holocene and a wet phase in the middle to late Holocene, followed by another dry phase. These data correspond well with published data of 2 phases of dune formation (dry periods) in the early to middle Holocene and in the latest Holocene for North Queensland.
Development of an equation to relate electrical conductivity to soil and water salinity in a Mediterranean agricultural environment
Authors: Reluy F. Visconti , Bécares J. M. de Paz , Hernández R. D. Zapata , Díaz J. Sánchez
Published: June 2004

A linear equation to relate total ionic concentration to electrical conductivity (EC) in natural aqueous systems from low to medium level salt content was derived from the theory of EC in aqueous solutions. Some of the empirical equations used in soil science to characterise the salinity of soil and water based on the EC can be reduced to that equation. Also, it can be seen that aqueous systems with different relative ionic compositions have different values for the regression coefficient that relates EC to total ionic concentration. The equation was validated on the basis of the Faraday constant with some soil saturation extracts and irrigation waters sampled in different places along the Valencian Community (eastern Spain, western Mediterranean basin), and with data from the literature. The validation was performed using the chemical speciation program SOILSOLN. The results of the validation improved when activities were considered instead of concentrations, and in more dilute aqueous systems. Finally, the validation showed that the formation of ion pairs in the aqueous systems analysed was negligible due to the relatively low concentrations of sulfate, magnesium, and calcium.
Leaching of macronutrients and metals from undisturbed soils treated with metal-spiked sewage sludge. 2. Leaching of metals
Authors: McLaren R. G. , Clucas L. M. , Taylor M. D. , Hendry T.
Published: June 2004

The extent of metal (Cd, Cr, Cu, Ni, Pb, Zn) leaching from soils treated with metal-spiked sewage sludge was examined using large undisturbed soil lysimeters of 5 different New Zealand soils (2 pasture and 3 forest soils). Metal leaching from the soils was monitored continuously over a period of 3 years following a single application of sewage sludge. Metal speciation in leachates was estimated using GEOCHEM-PC. Application of the sludge resulted in decreased pH and increased concentrations and total amounts of Cd, Ni, and Zn in drainage leachates from some of the soils, but had little effect on, or decreased concentrations of, Cr, Cu, and Pb. In the case of Cu, and to a lesser extent Pb, the reduced leaching of these metals in the forest soils was considered related to the lack of plant cover and reduced pH and soluble organic C in leachates from the sludge-treated lysimeters. The peaking of Ni and Zn concentrations well before 1 pore volume of water had passed through the lysimeters indicated that macropore flow was an important process facilitating the leaching of these metals. The extent of metal leaching varied greatly between soils and was dependent on a number of soil properties and other factors, including plant cover (pasture v. forest soils). However, even under the extreme conditions of the study, very small proportions (~1% or less) of the applied metals were leached over the 3-year period. In some cases, Ni and Zn concentrations in drainage leachates exceeded drinking water and/or environmental standards. However, with further attenuation and dilution in the vadose zone, in the short-term at least, the leaching of these metals would seem unlikely to pose a major environmental threat.
Donor-specific transplantation tolerance: The paradoxical behavior of CD4+CD25+T cells
Authors: Graca Luis , Le Moine Alain , Lin Chun-Yen , Fairchild Paul J. , Cobbold Stephen P. , Waldmann Herman
Published: June 2004

To investigate the antigen specificity of regulatory T cells capable of preventing transplant rejection, we have developed two different strategies to achieve tolerance to fully mismatched skin grafts in euthymic mice. A combination of nondepleting Abs targeting CD4, CD8, and CD154 (CD40 ligand) induces dominant transplantation tolerance to fully mismatched skin allografts. Such tolerance is antigen-specific, mediated by regulatory T cells, and can be extended through linked suppression to naïve lymphocytes. The same protocol, when combined with allogeneic bone marrow, enables the development of mixed hematopoietic chimerism and deletional tolerance. Although we cannot exclude that some regulatory T cells may persist in chimeric mice, these cells are insufficient to mediate linked suppression. CD4+CD25+T cells, whether taken from naïve mice or from mice tolerized through either treatment protocol, were always able to prevent rejection of skin grafts by naïve CD4+T cells, and did so with no demonstrable specificity for the tolerizing donor antigens. Such data question whether CD4+CD25+regulatory T cells alone can account for the antigen specificity of dominant transplantation tolerance.
Stochastic computing with biomolecular automata
Authors: Adar Rivka , Benenson Yaakov , Linshiz Gregory , Rosner Amit , Tishby Naftali , Shapiro Ehud
Published: June 2004

Stochastic computing has a broad range of applications, yet electronic computers realize its basic step, stochastic choice between alternative computation paths, in a cumbersome way. Biomolecular computers use a different computational paradigm and hence afford novel designs. We constructed a stochastic molecular automaton in which stochastic choice is realized by means of competition between alternative biochemical pathways, and choice probabilities are programmed by the relative molar concentrations of the software molecules coding for the alternatives. Programmable and autonomous stochastic molecular automata have been shown to perform direct analysis of disease-related molecular indicators
in vitro
and may have the potential to provide
in situ
medical diagnosis and cure.
The specific binding of retinoic acid to RPE65 and approaches to the treatment of macular degeneration
Authors: Gollapalli Deviprasad R. , Rando Robert R.
Published: June 2004

RPE65 is essential in the operation of the visual cycle and functions as a chaperone for all-
trans
-retinyl esters, the substrates for isomerization in the visual cycle. RPE65 stereospecifically binds all-
trans
-retinyl esters with a
K
D
of 47 nM. It is shown here by using a quantitative fluorescence technique, that Accutane (13-
cis
-retinoic acid), a drug used in the treatment of acne but that causes night blindness, binds to RPE65 with a
K
D
of 195 nM. All-
trans
-retinoic acid binds with a
K
D
of 109 nM. The binding of the retinoic acids to RPE65 is competitive with all-
trans
-retinyl ester binding, and this competition inhibits visual cycle function. A retinoic acid analog that binds weakly to RPE65 is not inhibitory. These data suggest that RPE65 function is rate-limiting in visual cycle function. They also reveal the target through which the retinoic acids induce night blindness. Finally, certain forms of retinal and macular degeneration are caused by the accumulation of vitamin A-based retinotoxic products, called the retinyl pigment epithelium–lipofuscin. These retinotoxic products accumulate during the normal course of rhodopsin bleaching and regeneration after the operation of the visual cycle. Drugs such as Accutane may represent an important approach to reducing the accumulation of the retinotoxic lipofuscin by inhibiting visual cycle function. The identification of RPE65 as the visual cycle target for the retinoic acids makes it feasible to develop useful drugs to treat retinal and macular degeneration while avoiding the substantial side effects of the retinoic acids.
Localized chemical release from an artificial synapse chip
Authors: Peterman Mark C. , Noolandi Jaan , Blumenkranz Mark S. , Fishman Harvey A.
Published: June 2004

A device that releases chemical compounds in small volumes and at multiple, well defined locations would be a powerful tool for clinical therapeutics and biological research. Many biomedical devices such as neurotransmitter-based prostheses or drug delivery devices require precise release of chemical compounds. Additionally, the ability to control chemical gradients will have applications in basic research such as studies of cell microenvironments, stem cell niches, metaplasia, or chemotaxis. We present such a device with repeatable delivery of chemical compounds at multiple locations on a chip surface. Using electroosmosis to drive flow through microfluidic channels, we pulse minute quantities of a bradykinin solution through four 5-μm apertures onto PC12 cells and show stimulation of individual cells using a Ca
2+
-sensitive fluorescent dye. We also present basic computational results with experimental verification of both fluid ejection and fluid withdrawal by imaging pH changes by using a fluorescent dye. This “artificial synapse chip” is a prototype neural interface that introduces a new paradigm for neural stimulation, with eventual application in treating macular degeneration and other neurological disorders.
Mass spectrometric characterization of a three-enzyme tandem reaction for assembly and modification of the novobiocin skeleton
Authors: Pi Na , Meyers Caren L. Freel , Pacholec Michelle , Walsh Christopher T. , Leary Julie A.
Published: June 2004

The tripartite scaffold of the natural product antibiotic novobiocin is assembled by the tandem action of novobiocin ligase (NovL) and novobiocic acid noviosyl transferase (NovM). The noviosyl ring of the tripartite scaffold is further decorated by a methyltransferase (NovP) and a carbamoyltransferase (NovN), resulting in the formation of novobiocin. To facilitate kinetic evaluation of alternate substrate usage by NovL and NovM toward the creation of variant antibiotic scaffolds, an electrospray ionization/MS assay for obtaining kinetic measurements is presented for NovL and NovM separately, in each case with natural substrate and the 3-methyl-4-hydroxybenzoic acid analog. Additionally, assays of tandem two-enzyme (NovL/NovM) and three-enzyme (NovL/NovM/NovP) incubations were developed. The development of these assays allows for the direct detection of each intermediate followed by its utilization as substrate for the next enzyme, as well as the subsequent formation of final product as a function of time. This MS tandem assay is useful for optimization of conditions for chemoenzymatic generation of novobiocin and is also suitable for evaluation of competitive usage of variant substrate analogs by multiple enzymes. The studies presented here serve as a platform for the subsequent expansion of the repertoire of coumarin-based antibiotics.
Single-molecule enzymology of RNA: Essential functional groups impact catalysis from a distance
Authors: Rueda David , Bokinsky Gregory , Rhodes Maria M. , Rust Michael J. , Zhuang Xiaowei , Walter Nils G.
Published: June 2004

The hairpin ribozyme is a minimalist paradigm for studying RNA folding and function. In this enzyme, two domains dock by induced fit to form a catalytic core that mediates a specific backbone cleavage reaction. Here, we have fully dissected its reversible reaction pathway, which comprises two structural transitions (docking/undocking) and a chemistry step (cleavage/ligation), by applying a combination of single-molecule fluorescence resonance energy transfer (FRET) assays, ensemble cleavage assays, and kinetic simulations. This has allowed us to quantify the effects that modifications of essential functional groups remote from the site of catalysis have on the individual rate constants. We find that all ribozyme variants show similar fractionations into effectively noninterchanging molecule subpopulations of distinct undocking rate constants. This leads to heterogeneous cleavage activity as commonly observed for RNA enzymes. A modification at the domain junction additionally leads to heterogeneous docking. Surprisingly, most modifications not only affect docking/undocking but also significantly impact the internal chemistry rate constants over a substantial distance from the site of catalysis. We propose that a network of coupled molecular motions connects distant parts of the RNA with its reaction site, which suggests a previously undescribed analogy between RNA and protein enzymes. Our findings also have broad implications for applications such as the action of drugs and ligands distal to the active site or the engineering of allostery into RNA.
THE RELATION OF FATTY DEGENERATION TO THE OXIDATION OF PURINES BY LIVER CELLS
Authors: Wells H. Gideon
Published: June 2004

These experiments show that it is possible to cause, by the proper use of hydrazine and phosphorus, a very high degree of fatty change in the liver with a minimum of necrosis, involving alike both peripheral and central portions of the lobule and thus eliminating the " factor of safety" or residual normal cells. Nevertheless, it is found that such fatty liver tissue has not lost in the least its power to oxidize uric acid when acting upon it in vitro with abundant air supply, nor is the power to oxidize xanthine to uric acid noticeably diminished. Since these two enzymes, and especially the uricolytic enzyme, are about the last to appear in the development of the animal kingdom and also of the individual mammal, it is to be expected that they will be among the first of the enzymes to be destroyed by injurious agencies, but evidently they are not affected by conditions that lead to the highest degree of fatty metamorphosis of the cytoplasm of the hepatic cells. While these experiments merely prove that extreme fatty degeneration does not destroy or appreciably diminish the power of liver cells to oxidize uric acid and xanthine in vitro, yet they suggest that in general fatty degeneration is probably not essentially incompatible with a high degree of metabolic activity by the affected cells. It is possible that in the living tissue functional activity may be decreased secondarily by fatty metamorphosis, as, for example, by the enlarged fatty cells compressing the capillaries and reducing circulatory activity, or by modification of diffusion through the cell by the fat deposits, independent of any deleterious influence upon the cellular enzymes themselves. Other experiments will be required to determine whether steatogenic poisons leave intrahepatic enzymes other than the uricase equally unaffected, but as it has already been shown by Jacoby that the autolytic enzymes and aldehydase in the liver cells are not destroyed by phosphorus poisoning, and Abderhalden and Schittenhelm* found that peptids are hydrolyzed fully as rapidly by phosphorus livers as by normal livers, it seems probable that extreme fatty metamorphosis is not associated with any serious injury to the enzymes by which the liver cells perform their metabolic functions, with the possible exception of those enzymes concerned with the metabolism of fats.
EXPERIMENTAL YAWS IN THE MONKEY AND RABBIT
Authors: Nichols Henry J.
Published: June 2004

1. Rabbits can be infected in the testicle with the spirochetæ of yaws as well as with those of syphilis and the infection can be continued through successive generations in pure culture.

2. The infection shows itself by enlargement of the testicle and the presence of a nodule varying in size from that of a pea to that of an olive. The infection consists in a necrosis of the tubules, an infiltration of round cells and the new formation of an edematous connective tissue.

3. The complement fixation reaction occurs in rabbits infected with the spirochetæ of yaws as well as in those infected with the spirochetæ of syphilis.

4. This lesion makes possible the investigation of the problems of cultivation, of immunity and of treatment.
CHANGES IN THE HEMOSIDERIN CONTENT OF THE RABBIT'S LIVER DURING AUTOLYSIS
Authors: Brown W. H.
Published: June 2004

1. Hemosiderin may be produced outside of the animal body and is increased in the liver of rabbits, during autolysis, for a period of from twenty-four to forty-eight hours.

2. Post-mortem hemosiderin formation is most marked in parts of livers exposed to air, and hemosiderin is, apparently, an oxidation product of hemoglobin due to enzyme action.

3. Hemosiderin is derived from hemoglobin directly and not from hematin as an intermediate product.

4. The later stages of autolytic changes show that the acid products of proteid autolysis, especially the phosphorus acids, are capable of producing a cleavage of hemosiderin and uniting with the iron to form a new series of products which react microchemically for both phosphorus and iron. In such cleavage, pigments analogous to the bile pigments are formed.

5. The relationship observed between hemosiderin and hematoidin is such as would indicate that hematoidin is the pigment matter of hemosiderin.

6. Further, it seems probable that the vital cycle of hemoglobin metabolism in the liver is largely intranuclear; the hemoglobin is converted into hemosiderin either within the nucleus or cell protoplasm; the iron of the hemosiderin is bound by an acid radicle of the nucleo-proteid, and the hematoidin is excreted as bile pigment.
Two loci affecting B cell responses to B cell maturation factors.
Authors: Sidman C L , Marshall J D , Beamer W G , Nadeau J H , Unanue E R
Published: June 2004

B lymphocytes from DBA/2Ha mice have a genetic defect characterized by a failure to differentiate into antibody-secreting cells in response to a family of lymphokines termed B cell maturation factors (BMFs). By contrast, B cells from DBA/2Ha mice respond normally in PFC assays to the B cell mitogen LPS, and macrophages from these mice are activated by one of the three BMFs. Two loci are responsible for the B cell defect in DBA/2Ha mice. One locus (Bmfr-1) is constitutively expressed throughout life, and maps approximately 13 cM distal to the brown locus on chromosome 4. A second locus (Bmfr-2) becomes active only after sexual maturity and is closely linked to the dilute locus on chromosome 9. At both loci, alleles determining responsiveness to BMFs are dominant over nonresponder alleles. The effect of Bmfr-2 on B cell responsiveness may be related to levels of the steroid sex hormones. DBA/2Ha mice offer a tool for studying the genetic and hormonal regulation of the immune system.
Human-human hybridomas secreting monoclonal antibodies to the Mr 195,000 Plasmodium falciparum blood stage antigen.
Authors: Schmidt-Ullrich R , Brown J , Whittle H , Lin P S
Published: June 2004

Using the human lymphoblastoid cell line, GM 4672, and PBL of Gambian adults immune to Plasmodium falciparum (Pf) malaria, we have produced human-human hybridomas and selected those that produce mAb against Pf antigens. The fusion frequency, using PWM-stimulated donor lymphocytes was between 6.8 X 10(-5) and 1.5 X 10(-6). Using immune fluorescence, immune precipitation, and Pf in vitro growth inhibition, we cloned four hybridomas that reacted with the Pf Mr 195,000 schizont/merozoite protein. The differences in proteins immune precipitated and in growth inhibition indicate that, during development of protective immunity against Pf malaria, a spectrum of antibodies is produced reacting with different epitopes on the same antigen. Only a portion of these antibodies exhibits biological activity, suggesting that the recognition of certain epitopes is required for the development of a protective immune response.
Direct interactions between B and T lymphocytes bearing complementary receptors.
Authors: Tite J P , Kaye J , Saizawa K M , Ming J , Katz M E , Smith L A , Janeway C A
Published: June 2004

A murine cloned Th cell line specific for the antigen conalbumin in the context of self I-A molecules can be activated by low concentrations of soluble antireceptor mAb. By using an antireceptor mAb to shared antigenic determinants on T cell receptors, we have shown that the ability to be activated by soluble antireceptor mAb is an unusual, although not unique, feature of this cloned T cell line. This activation does not involve occult APC, FcR, or interaction between individual cloned T cells, as limiting-dilution analysis shows that individual cells of this clone will grow in the presence of the antireceptor antibody and IL-1 as stimulus. This cloned T cell line is highly immunogenic in vivo, giving rise to antireceptor antibodies that stimulate its growth in both mice and rats. This response is not dependent upon exogenous T cells. Rather, the clone directly interacts with complementary B cells, as shown by the production of mAb in nude mice, and by production of stimulating antireceptor antibodies by purified B cells cultured with cloned Th cells in vitro. Several features of this cloned Th cell line, most especially its ability to be activated, rather than inhibited, by antireceptor antibodies, may account for its striking ability to directly activate B cells bearing complementary receptors. The direct interaction of the cloned Th cell with B cells bearing complementary receptors may serve as a model for receptor-receptor interactions in the generation of both T and B cell repertoires.
Crossprotection against nontuberculous mycobacterial infections by Mycobacterium tuberculosis memory immune T lymphocytes.
Authors: Orme I M , Collins F M
Published: June 2004

Adoptive immunization of T cell-deficient recipient mice with M. tuberculosis-specific memory immune T lymphocytes conferred upon these animals the ability to express significantly enhanced resistance both to the homologous infection, and to three strains of nontuberculous mycobacteria. These results support the hypothesis, therefore, that antigenic determinants possessed by the four mycobacterial strains that are relevant to the generation of protective cellular immunity are identical or closely crossreactive.
Human natural killer cells isolated from peripheral blood do not rearrange T cell antigen receptor beta chain genes.
Authors: Lanier L L , Cwirla S , Federspiel N , Phillips J H
Published: June 2004

The lineage of NK cells and their relationship to T lymphocytes have been controversial issues. Since rearrangement of the T cell antigen receptor beta chain genes occurs early in the ontogeny and differentiation of all T cells, this can be used as an unequivocal marker to discriminate T from non-T lymphocytes. Recent studies (16-18) examining T cell antigen receptor gene rearrangement and expression in certain IL-2-dependent NK cell lines and leukemias have revealed that some lines rearrange C beta genes, whereas others do not. However, it is important to establish whether these cell lines are representative of the major population of NK cells freshly derived from the host. Herein, we have purified granulocytes, CD16+ NK cells and T lymphocytes from human peripheral blood, prepared genomic DNA from each cell type, and then examined the organization of their T cell antigen receptor genes by restriction enzyme analysis using a C beta cDNA as probe. The C beta genes were in germline configuration in NK cells and granulocytes. In contrast, peripheral blood T lymphocytes showed rearrangement of the C beta gene. These data support the hypothesis that the majority of human peripheral blood NK cells are fundamentally distinct from T lymphocytes in lineage and nonself recognition.
Regulation of T cell autocrine growth. T4+ cells become refractory to interleukin 2.
Authors: Gullberg M , Smith K A
Published: June 2004

During the course of investigating the regulation of IL-2-dependent T cell proliferation, we found that the subset of human T cells expressing the T4 surface glycoprotein become refractory to IL-2 growth promotion earlier than T8+ cells. Since T4+ cells proliferate in an autocrine fashion to endogenous IL-2, whereas most T8+ cells respond in a paracrine fashion to IL-2 derived from T4+ cells, we thought it likely that a unique mechanism was operative to restrict T4+ cell IL-2-dependent autocrine proliferation. Moreover, we anticipated that the T4+ cell IL-2-refractory state related either to suppression by T8+ cells, or to expression of T4+ cell IL-2-R. However, several experimental approaches did not support either of these mechanisms as being responsible for the loss of T4+ cell IL-2 responsiveness. Isolated T4+ cells ceased to respond to IL-2 well before T8+ cells, and before the disappearance of adequate levels of IL-2-R. Moreover, a detailed comparison of IL-2-R expression by T4+ vs. T8+ cells revealed no differences in the number, affinity, rate of expression, or functional activity of high-affinity IL-2-R expressed by the two subsets. Accordingly, T4+ cell autocrine IL-2 responsiveness is restricted by a mechanism that is independent of IL-2-R, and which ultimately results in cessation of both T4+ and T8+ cell IL-2-dependent clonal expansion.
Influence of the murine MHC (H-2) on Friend leukemia virus-induced immunosuppression.
Authors: Morrison R P , Nishio J , Chesebro B
Published: June 2004

Friend murine leukemia virus complex (FV)-induced immunosuppression was studied by assaying splenic anti-SRBC PFC responses and plasma antibody titers in mice at various times after FV inoculation. Genes located within the H-2 complex were found to influence resistance to FV-induced immunosuppression. Near normal responses were observed in mice having the H-2a/b or H-2b/b genotype, whereas mice having the H-2a/a genotype were suppressed. This H-2 effect was observed not only in mice having heterozygous C57BL/10 X A background genes, including Rfv-3r/s, but also was apparent in mice having homozygous A-strain background genes, including Rfv-3s/s. Therefore, the Rfv-3 gene did not appear to convey resistance to FV-induced immunosuppression. The suppression in susceptible H-2a/a mice was characterized by a partial suppression of the IgM response and a profound suppression of both the primary and secondary IgG responses. Neither splenomegaly nor viremia alone appeared to be sufficient for the induction or maintenance of the immunosuppression. The mechanism of suppression was unclear, but both B lymphocyte and T lymphocyte functions appeared to be altered.
Configuration and expression of the T cell receptor beta chain gene in human T-lymphotrophic virus I-infected cells.
Authors: Jarrett R F , Mitsuya H , Mann D L , Cossman J , Broder S , Reitz M S
Published: June 2004

We studied the configuration and expression of the gene encoding the beta chain of the T cell receptor (TCR beta) in cell lines and primary tumor cells infected by the human T cell leukemia/lymphoma (lymphotrophic) virus type I (HTLV-I). Most of the cell lines and all the primary tumor cells showed rearrangement of the TCR beta gene, and in each case the rearrangement was distinct. The majority of cases examined were clonal with respect to a particular TCR beta gene rearrangement. Primary tumor cells from one case (SD) were found to have a tandem duplication of a portion of chromosome 7; this appears to have resulted in the presence of three alleles of the TCR beta gene, each of which is arranged differently. This suggests that the chromosomal abnormality, and possibly infection by HTLV-I, occurred before TCR beta gene rearrangement. Cell lines infected by HTLV-I express levels of TCR beta mRNA similar to PHA stimulated lymphocytes, suggesting that this gene is not transcriptionally activated as a result of infection by HTLV-I. Cloned T cells of known antigen specificity that are infected by HTLV-I in vitro show impairment of immune function, including loss of antigen-specific responsiveness and the acquisition of alloreactivity. Comparison of the configuration of the TCR beta gene before and after infection revealed no changes detectable by Southern blot analysis. Levels of expression of the TCR beta gene at the mRNA level and surface expression of the T3 complex were also not significantly altered, suggesting that changes in immune function cannot be attributed to quantitative changes in the TCR molecule. The configuration of the TCR beta gene in primary tumor cells infected by HTLV-I was compared with that in the derived cell lines. In all pairs examined, the configuration in the primary tumor cells was different from that in the cell lines, strongly suggesting that the cells that grow in culture are not the original neoplastic cells.
Characterization of rabbit stromal fibroblasts derived from red and yellow bone marrow.
Authors: Bainton D F , Maloney M A , Patt H M , Stern R
Published: June 2004

Rabbit stromal fibroblasts subcultured from red and yellow bone marrow and implanted beneath the renal capsule form ossicles the hemic cellularity of which mirrors the cellularity of the marrow used for culture. Although the cultured red and yellow marrow cells are similar in fine-structural appearance, they differ strikingly in enzymatic content of alpha-naphthylbutyrate esterase, which is abundant only in the cells derived from yellow marrow. Other observers (20, 21) have proposed that stromal fibroblasts are preadipocytes, and this data suggests that those derived from yellow marrow have the phenotype of more differentiated adipocytes. On the other hand, fibroblasts derived from red and yellow bone marrow show no differences in their profiles of procollagen synthesis. Both types of fibroblasts secrete type III procollagen as the major species, with a I/III ratio of 1:3; in contrast, rabbit dermal fibroblasts have a prominent peak of type I procollagen. The similarity of stromal cells derived from red and yellow bone marrow in procollagen synthesis suggests that the collagen part of the extracellular matrix is not the only basis for their intrinsic difference in capacity for hematopoiesis.
T cell receptor and immunoglobulin gene rearrangements in acute myeloblastic leukemia.
Authors: Cheng G Y , Minden M D , Toyonaga B , Mak T W , McCulloch E A
Published: June 2004

The organization and expression of the beta chain of T cell antigen receptor gene (beta-TCR) and Ig H and L chain genes were analyzed by Southern blot technique in 24 patients with a diagnosis of acute myeloblastic leukemia (AML). Rearrangements of the beta-TCR genes were seen in DNA samples from 3 of the 24 patients. One of these three patients also showed rearrangement of the Ig H chain gene. RNA samples from all three patients expressed a beta-TCR gene transcript on dot blot analysis. However, on Northern blot analysis, one patient expressed an incomplete 1.0 kb transcript and no Ig H chain mRNA, despite a rearranged configuration. The karyotypes of two of these patients showed abnormalities involving chromosome 7. Rearrangements of T cell antigen receptor genes may occur in nonlymphoid malignancy, and is consistent with the concept of lineage infidelity in AML.
Cell surface antigens of murine leukemias induced by radiation leukemia virus. Recognition of individually distinct cell surface antigens by cytotoxic T cells on leukemias expressing crossreactive transplantation antigens.
Authors: Morishita H , Shiku H , Horibe K , Obata Y , Stockert E , Oettgen H F , Old L J , Yamada K
Published: June 2004

The specificity of transplantation immunity and T cell cytotoxicity against leukemias induced by RadLV was examined. Subcutaneous inoculation of two RadLV leukemias induced in BALB/c mice, BALBRVB and BALBRVD, resulted in initial tumor growth in CB6F1 mice, followed by complete tumor regression. Mice that had rejected leukemias BALBRVB or BALBRVD were subsequently challenged with various tumors of BALB/c origin. The growth of all five RadLV leukemias tested, and of one radiation-induced leukemia, was significantly inhibited. Another radiation-induced leukemia, a methylcholanthrene-induced sarcoma, and a leukemia induced by the Moloney leukemia virus, were not inhibited. The results indicate that RadLV leukemias share cell surface antigens that induce transplantation immunity in vivo. Cytotoxic lymphocytes were generated by coculturing spleen cells from mice that had rejected leukemia BALBRVB or BALBRVD with the corresponding leukemia cells. Direct tests and inhibition tests showed that such cytotoxic cells recognized individually specific antigens on leukemias BALBRVB and BALBRVD, distinct from the shared antigens detected in transplantation experiments. The effector cells in cytotoxicity assays were Thy-1+, Lyt-1+,-, Lyt-2+, and Lyt-3+ T cells.
Immunogenicity and crossreactivity of specificity-associated markers on alloreactive T cells. Confirmation based on the model of tolerance abolition by adoptive transfer.
Authors: Kimura H , Silvers W K , Wilson D B
Published: June 2004

Syngeneic or parental strain T cells adoptively transferred into hybrid rats tolerant of third party alloantigens (L/DA tolerant of BN), in numbers insufficient to abolish tolerance, induce instead an active resistance to tolerance abolition with larger, usually effective dosages of donor cells. Of particular interest is the finding that immunization with T cells from one parental strain donor (e.g., DA) inhibited the tolerance-abolishing alloreactivity (anti-BN) of subsequently transferred T cells from the same (DA) and the other (L) parental strain donor. We conclude that anti-MHC receptors on T cells from different genetic backgrounds reactive to the same third party alloantigens share the same conserved immunogenic specificity-associated markers (SAM). The nonpolymorphism of anti-MHC receptors shown here in the transplantation tolerance model is a confirmation of the same conclusion drawn from earlier studies with the GVHD-resistance model, and it therefore suggests that these two models of T cell MHC interactions involve very similar mechanisms of T cell idiotypic regulation.
Interleukin 1 and interleukin 1 inhibitor production by human macrophages exposed to influenza virus or respiratory syncytial virus. Respiratory syncytial virus is a potent inducer of inhibitor activity.
Authors: Roberts N J , Prill A H , Mann T N
Published: June 2004

Respiratory viral infections are commonly associated with altered immune responses, such as proliferative responses to mitogens and antigens. To examine potential mechanisms, we examined production of IL-1 and IL-1 inhibitors by purified human peripheral blood-derived macrophages exposed to influenza virus or respiratory syncytial virus (RSV). IL-1 and IL-1 inhibitor activities in supernatant fluids from macrophages exposed to the viruses 24 h previously were measured using the standard mouse thymocyte comitogen assay. Crude fluids from macrophages exposed to influenza virus contained substantial IL-1 activity, whereas crude fluids from macrophages exposed to RSV contained marked IL-1 inhibitor activity. Assays with gel filtration-separated fractions revealed that both influenza virus and RSV induced production of both IL-1 and IL-1 inhibitors. Neither IL-2 nor IL-2 inhibitor activities were detected. Thus, effects of human macrophage-derived factors on thymocyte proliferation, or potentially on human lymphocyte proliferation, may reflect the total or net activity of multiple composite factors, the balance of which varies according to the challenge. The data raise the possibility that marked production of IL-1 inhibitor activity in response to RSV plays a role in the clinical recurrence of RSV infection despite the absence of clear evidence for antigenic shift or drift of the virus.