bluuebunny/crossref_metadata_2025 huggingface dataset:
mRNA expression and protein distribution of the unspliced tenascin‐C isoform in prostatic adenocarcinoma
Authors: Katenkamp Kathrin , Berndt Alexander , Hindermann Winfried , Wunderlich Heiko , Haas Karl Michael , Borsi Laura , Zardi Luciano , Kosmehl Hartwig
Published: June 2004

The inclusion or omission of the alternatively spliced region in the tenascin‐C (Tn‐C) mRNA gives rise to the large (Tn‐CL) or small (Tn‐CS) variant, respectively. Tn‐CL is thought to be a typical component of provisional extracellular matrices (ECMs) and is expressed during tumour stroma remodelling in cancer. Tn‐CL mRNA expression and protein distribution have been studied in 44 prostatic adenocarcinomas using RNA/RNA in situ hybridization supplemented by reverse transcriptase‐polymerase chain reaction (RT‐PCR), and immunohistochemistry (clone BC‐2). While the Tn‐CL protein was demonstrated within tumour stroma, Tn‐CL mRNA expression was mainly observed in carcinoma cells, regardless of the histological grade of the tumour. Carcinoma cells containing Tn‐CL mRNA were particularly localized at the tumour invasion front. Tn‐CL mRNA was also identified in benign prostatic hyperplasia, where it was present exclusively in the basal cell layer, and in prostatic intraepithelial neoplasia in which there was partial loss of positive basal cells and increasing positivity of luminal cells. Furthermore, newly formed tumour blood vessels and inflammatory and stromal cells take part in the expression of Tn‐CL and are involved in the formation of a provisional tumour matrix. It is concluded that deposits of Tn‐CL indicate rebuilding processes in non‐neoplastic as well as in neoplastic prostatic tissues. In respect of the Tn‐CL synthesis in budding prostatic carcinoma cells, the results demonstrate that tumour cells can directly produce the ECM components of carcinoma stroma, creating conditions that facilitate the process of invasion. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Expression of heat shock protein 27 in human renal cell carcinoma
Authors: Sarto Cecilia , Valsecchi Cristina , Magni Fulvio , Tremolada Lucia , Arizzi Carmelo , Cordani Nicoletta , Casellato Stefano , Doro Giancarlo , Favini Paolo , Perego Roberto A. , Raimondo Francesca , Ferrero Stefano , Mocarelli Paolo , Galli‐Kienle Marzia
Published: June 2004

Heat shock protein 27 (HSP27, Swiss‐Prot accession number P04792) is a component of the large and heterogeneous group of chaperone proteins, and its main functions are inhibition of apoptosis and prevention of aggregation of actin intermediate filament. Modified expression of HSP27 has been described in several cancers including testis, breast, and ovaric cancer. In the present work, 18 renal cell carcinoma (RCC) tissues and homologous normal kidney tissues have been investigated for HSP27 expression by combination of two‐dimensional polyacrylamide gel electrophoresis (2‐D PAGE) separation and Western blotting immunodetection. The results showed significant differences either in expression and in HSP27 isoform numbers in RCC compared to normal kidney. The average number of isoforms was 21 in RCC and 15 in normal tissues with 4.5–5.9 pI range and 18–29 kDa Mr range. The overexpression was also observed by immunohistochemistry on tissue sections. Only two of RCC samples showed less isoforms than homologous normal samples. Two isoforms were not detected using anti‐Ser82 phosphorylated HSP27 antibody, neither in normal nor in RCC samples. Five of all the immunodetected isoforms were confirmed by mass spectrometry as HSP27, but no evidence of post‐translational modifications was pointed out. The numerous isoforms observed in RCC are not consistent with data reported in the literature so far, and they might be due to different post‐translational modifications such as phosphorylation and S‐thiolation. Since activation of HSP27 seems to be involved in tumor proliferation and drug resistance, it would be crucial to correlate the severity of disease with the different isoforms from RCC samples to generate diagnostic and prognostic markers.
ApoC‐I and ApoC‐III as potential plasmatic markers to distinguish between ischemic and hemorrhagic stroke
Authors: Allard Laure , Lescuyer Pierre , Burgess Jennifer , Leung Kit‐Yi , Ward Malcolm , Walter Nadia , Burkhard Pierre R. , Corthals Garry , Hochstrasser Denis F. , Sanchez Jean‐Charles
Published: June 2004

Early diagnosis and immediate therapeutic interventions are crucial factors to reduce the damage extent and the risk of death. Currently, the diagnosis of stroke relies on neurological assessment of the patient and neuro‐imaging techniques including computed tomography and/or magnetic resonance imaging scan. An early diagnostic marker of stroke, ideally capable to discriminate ischemic from hemorrhagic stroke would considerably improve patient acute management. Using surface‐enhanced laser desorption/ionization (SELDI) technology, we aimed at finding new early diagnostic plasmatic markers of stroke. Strong anionic exchange (SAX) SELDI profiles of plasma samples from 21 stroke patients were compared to 21 samples from healthy controls. Seven peaks appeared to be differentially expressed with significant p values (p < 0.05). Proteins were stripped from the SAX chips, separated on a one‐dimensional electrophoresis (1‐DE) gel and stained using mass spectrometry (MS)‐compatible silver staining. Following in‐gel tryptic digestion, the peptides were analyzed by MS. Four candidate proteins were identified as apolipoprotein CI (ApoC‐I), apolipoprotein CIII (ApoC‐III), serum amyloid A (SAA), and antithrombin‐III fragment (AT‐III fragment). Assessment of ApoC‐I and ApoC‐III levels in plasma samples using a sandwich enzyme‐linked immunosorbent assay (ELISA) allowed to distinguish between hemorrhagic (n = 15) and ischemic (n = 16) stroke (p < 0.001). To the best of our knowledge, ApoC‐I and ApoC‐III are the first reported plasmatic biomarkers capable to accurately distinguish between ischemic and hemorrhagic stroke in a small number of patients. It requires further investigation in a large cohort of patients.
Some physical properties of polyorganosiloxanes. I. Linear polyorganosiloxanes
Authors: Andrianov K. A. , Slonimskiĭ G. L. , Zhdanov A. A. , Yu. Levin V. , Godovskiĭ Yu. K. , Moskalenko V. A.
Published: June 2004

Some physical properties of linear polydimethylsiloxanes have been studied. The states and transitions in polydimethylsiloxanes have been investigated by using the method of dynamic heat capacity and a thermomechanic method in the temperature range from −150 to +200°C. The temperature dependence of primary and secondary crystallization has been studied by optical, calorimetric, and x‐ray methods.
Molecular parameters of sodium amylose xanthate in dilute solution
Authors: Manna P. K. , Choudhury P. K.
Published: June 2004

Molecular parameters of sodium amylose xanthate in 1N NaOH solution have been determined by means of light scattering and viscometry. The expansion factor, α, has been determined from the expression due to Orofino and Flory. The value of a of the Mark‐Houwink relation, [η] = KMa, has been determined. The Stockmayer‐Fixman relationship has been used to evaluate the unperturbed dimension of the chain. The effective bond length b, Kuhn‐Kuhn equivalent chain segment length Am and the steric factor σ, i.e., the ratio of the unperturbed dimension to the dimension assuming free rotation of the chain \documentclass{article}\pagestyle{empty}\begin{document}$(\bar R_o^2 )_z ^{1/2} /(\bar R_f^2 )^{1/2}$\end{document} have also been determined. From these data, it is concluded that sodium amylose xanthate in 1N NaOH solution behaves as a loosely coiled molecule.
Cationic copolymerization of anethole: Reactivity of geometric isomers of α,β‐disubstituted ethylenes
Authors: Higashimura T. , Kawamura K. , Masuda T.
Published: June 2004

Cationic copolymerizations of anethole were carried out under various conditions in order to confirm the relative reactivities of its geometric isomers. trans‐Anethole was more reactive than cis‐anethole in copolymerizations with p‐methoxystyrene or styrene, but less reactive in the mutual copolymerization of cis‐ and trans‐anethole; i.e., the trans isomer was more reactive to a growing chain end with little steric hindrance. Thus the intrinsic reactivity of an olefinic double bond to carbonium ion is greater for the trans isomer than for the cis isomer. This idea is supported by 13C NMR spectra, since the signal of the olefinic β‐carbon of the trans isomer is at higher field than that of the cis isomer. The behavior of anethole was compared with the results observed in vinyl ethers, where the cis isomer was always more reactive irrrspective of the structure of the growing chain end. In addition, the dependence of monomer reactivity ratios on polymerization conditions is discussed.
Photosensitized dehydrochlorination of poly(vinyl chloride)
Authors: Owen E. D. , Bailey R. J.
Published: June 2004

The mechanism of the benzophenone‐photosensitized degradation of films of poly‐(vinyl chloride) was studied, both under vacuum and in the presence of oxygen. Initial rapid increases in absorption in the 340 nm region strongly implicate the ketyl radical in the initiation process which involves the abstraction by triplet benzophenone of a methylenic hydrogen from poly(vinyl chloride). Dehydrochlorination then occurs by a chain mechanism, and the conjugated polyene structure produced photosensitizes further initiation and, in the presence of oxygen, photo‐oxidation of the polymer.
Electron spin resonance study of poly‐3,3‐bis‐(chloromethyl)oxetane irradiated with ultraviolet light
Authors: Tsuji Kozo , Seiki Toshifumi
Published: June 2004

When poly‐3,3‐bis(chloromethyl)oxetane has been irradiated at −196°C in a nitrogen atmosphere with ultraviolet light, a triplet spectrum is observed. After warming the sample, both a doublet and a singlet ESR spectra are observed. These spectra are attributed to and CH2O, respectively. The formation mechanism of these free radicals is discussed. It is concluded that the main process of radical formation is the dissociation of chemical bonds from the excited state of the polymer produced through the energy absorption by irregular groups acting as sensitizers. In the presence of oxygen, the radical yield at −196°C is greater than that in nitrogen atmosphere. This is attributed to the extra absorption of light by the charge transfer complexes of polymers with oxygen molecules. It is also proposed that participation of a charge transfer complex in photooxidation of ether is important in the primary radical formation step. When a polymer sample irradiated in vacuum with ultraviolet light is treated at −78°C for a few minutes in the presence of air, peroxy radicals form. This shows that oxygen molecules diffuse very easily into this polymer, even at this low temperature.
Cyclopolymerization of divinyl esters of dibasic acids and structure of poly(vinyl alcohol) derived from the polymers
Authors: Kikukawa Kiyoshi , Nozakura Shun‐Ichi , Murahashi Shunsuke
Published: June 2004

Divinyl esters of dibasic acids, CH2CHOCO(CH2)n−2COOCHCH2, n = 2–10, were synthesized and polymerized with a radical initiator, and the structure of poly(vinyl alcohol)(PVA) derived from the polymers were studied. The cyclopolymerizability of these monomers was nearly equal to or less than that of divinyl carbonate which was previously reported, and the extent of cyclization was 15–65%. All the monomers yielded gelled polymers. The monomers which are to yield even‐membered rings tend to cyclopolymerize more easily than those of odd‐membered rings. PVA derived from these polymers showed a similar structure with respect to 1,2‐glycol content and stereoregularity to that from poly(vinyl acetate).
Formation of block copolymers from polyurethanes containing reactive disulfides
Authors: Fildes F. J. T. , Tobolsky A. V.
Published: June 2004

Block copolymers containing polyether segments and segments of a vinyl polymer have been synthesized. A low molecular weight polyether terminated with isocyanate groups was condensed with bis‐(β‐hydroxyethyl disulfide) to give polyurethanes containing reactive disulfide linkages. When this polymer was photolyzed in the presence of a vinyl monomer such as styrene, methyl methacrylate, or acrylonitrile, homolytic cleavage of the disulfide polymerized the monomer, giving block copolymers. The mechanical properties of the products were investigated by means of modulus–temperature measurements.
Universal calibration in GPC
Authors: Rudin Alfred , Hoegy Howard L. W.
Published: June 2004

The M[η]‐elution volume calibration curve for gel‐permeation chromatography (GPC) is based on the implicit assumption that the hydrodynamic volume of a solvated polymer species in the GPC columns is that which pertains at infinite dilution. This is not true of highly solvated high molecular weight fractions and results in apparent failure of this calibration in some instances. A model is presented to estimate hydrodynamic volumes of polymers at finite concentrations. The parameters required are polymer concentration, molecular weight, amorphous density, and the Mark‐Houwink constants for the particular polymer–solvent combination. The calculated log (hydrodynamic volume)–elution volume relation provides a universal GPC calibration. The model accounts for the occasional shortcomings of the infinite dilution calibration and is essentially equivalent to it in noncritical cases. The use of the proposed calibration method is illustrated.
Polymerizations of vinyl methacrylate and vinyl acrylate
Authors: Fukuda Wakichi , Nakao Masahiro , Okumura Kinichi , Kakiuchi Hiroshi
Published: June 2004

Both vinyl methacrylate (VMA) and vinyl acrylate (VA) were homopolymerized by n‐butyllithium catalyst at −78°C. Both of the anionic polymers were soluble in common organic solvents, and only vinyl group was contained in the polymers. Both of the monomers were homopolymerized by free‐radical catalysts under different conditions. The soluble polymers were obtained under low monomer concentrations and at low conversions. It was estimated by NMR and infrared spectroscopy that both the soluble polymers contained mainly a vinyl group, similar to the anionic polymers. The soluble VMA polymers comprised 10–20% cyclic units for monomer concentrations ranging from 1.8 to 0.5 mole/I. The soluble VA polymers comprised 50–60% cyclic units for monomer concentrations ranging from 0.9 to 0.3 mole/l. It was suggested that the cyclic units did not consist of γ‐lactone but of larger‐membered rings than δ‐lactone or of ladder structural units. The difference between the cyclization content of poly‐VMA and that of poly‐VA might be explained by the copolymerization data of the reference monomers.
Oxidation of polyethylene, polypropylene, and copolymers
Authors: Van Sickle Dale E.
Published: June 2004

This investigation of the autoxidation of ethylene–propylene copolymers and polyethylene–polypropylene mixtures was undertaken to determine whether reactivity is a linear function of composition. The copolymers and the mixtures were autoxidized in a trichlorobenzene solution at 100°C in the presence of 1,1′‐azodicyclohexanecarbonitrile, and the rates of oxygen absorption were determined. The reactivity of the copolymers and the mixtures, after the underlying absorption of oxygen by initiator radicals is accounted for, is a nearly linear function of composition; however, the polymer mixtures and copolymers oxidized somewhat less readily than predicted by a straight line relationship. Several additional oxidations were performed on solutions of polypropylene so that the effects of initiation rate and substrate concentration could be evaluated. The oxidation kinetics of polypropylene even in dilute solution, are complex; titratable hydroperoxide yields are low. Further work will be required to specify the mechanism of oxidation.
Dynamics of spherulitic growth in blends of polypropylene isomers
Authors: Mehta Rujul , Kyu Thein
Published: June 2004

The spatiotemporal growth of spherulites in blends of isotactic polypropylene (iPP) and atactic polypropylene (aPP) isomers has been investigated theoretically with the time‐dependent Ginzburg–Landau equation, which consists of a nonconserved crystal order parameter and a conserved compositional order parameter. In the description of the total free energy, a local free energy density in the form of an asymmetrical double well, signifying the metastability and latent heat of crystallization, is combined with a nonlocal free energy term representing the interface gradient. In addition, the Flory–Huggins free energy for mixing between iPP and aPP isomers has been employed to account for blend miscibility. Two‐dimensional simulations have been carried out, based on the known material parameters of blends of iPP and aPP. The rejection of aPP from the growing spherulitic front has been modeled for comparison with the reported experimental observations. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2892–2899, 2004
A new thermoplastic vulcanizate (TPV)/organoclay nanocomposite: Preparation, characterization, and properties
Authors: Mishra Joy K. , Kim Gue‐Hyun , Kim Il , Chung In‐Jae , Ha Chang‐Sik
Published: June 2004

The preparation, characterization, and properties of the new thermoplastic vulcanizate (TPV)/organoclay nanocomposites are reported in this article. The nanocomposites were prepared by the melt intercalation method. The organoclay was first treated with glycidyl methacrylate, which acts as a swelling agent for organoclays, as well as a grafting agent for TPV (in the presence of dicumyl peroxide) during the melt mixing. The nanocomposite was intercalated, as evidenced by X‐ray diffraction. The tensile modulus of the 5% TPV/organoclay nanocomposite was higher than that of the 20% talc‐filled microcomposite. The storage modulus of the nanocomposite was higher than that of the pristine TPV. The most important observation is obtained from dynamic mechanical analysis, which reveals that the glass‐transition temperature of the polypropylene phase of the nanocomposite increases (as compared to virgin TPV), whereas the ethylene–propylene–diene monomer phase remains almost the same. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2900–2908, 2004
Impact of a 100‐year flood on vegetation, benthic invertebrates, riparian fauna and large woody debris standing stock in an alpine floodplain
Authors: Hering Daniel , Gerhard Marc , Manderbach Randolf , Reich Michael
Published: June 2004

This paper investigates the impact of a 100‐year flood in May 1999 on community composition and large woody debris standing stock in an alpine floodplain (Isar, Germany). Detailed pre‐flood data sampled from 1993 to 1998 are compared with the situation directly after the flood. In those parts of the Isar floodplain mainly covered with pioneer vegetation prior to flooding, the coverage of unvegetated gravel bars increased by 22% following the flood. However, the flood did not remove larger amounts of older successional vegetation stages (willow thickets, floodplain forest). No significant changes in the benthic invertebrate fauna were recorded. The lowest densities of riparian ground beetles (Carabidae) within the study were recorded one month after the flood. Two months later, the ground beetle densities increased to the highest values ever recorded, indicating the ground beetle's high potential for recolonization. These results highlight the degree of resilience of both the aquatic and the riparian invertebrate fauna. The flood also caused a significant increase in large woody debris standing stock; in one section the number of logs increased tenfold and the volume increased by a factor of 20, leading to the assumption that most woody debris in alluvial flood‐plains is provided by catastrophic events. Copyright © 2004 John Wiley & Sons, Ltd.
Differences in intramembrane particle distribution in young and old human erythrocytes
Authors: Cordero Julio F. , Rodrıguez Pedro J. , Romero Pedro J.
Published: June 2004

The distribution of intramembrane particles in human erythrocytes was studied by freeze‐fracture on young and old cells and compared to that obtained after ATP depletion or following addition of a clustering agent. It was shown that intramembrane particles became aggregated and the mean particle density increased as the cells aged. Likewise, both particle aggregation and increased density were found in young cells after moderate ATP depletion. In contrast, mean particle density was markedly reduced in both cell types after exhaustive depletion. Paradoxically, Zn treatment led to decreased particle density in young cells, whilst producing the opposite effect in aged cells. The results suggest that their low ATP content may account for the increased particle density of senescent cells.
Synchronizing strict-feedback chaotic system via a scalar driving signal
Authors: Chen Shihua , Wang Dongxiao , Chen Li , Zhang Qunjiao , Wang Changping
Published: June 2004

We propose a systematic design procedure to synchronize a class of chaotic system in a so-called strict-feedback form based on back-stepping procedure. This approach needs only a scalar driving signal to realize synchronization no matter how many dimensions the chaotic system contains. Furthermore, the numerical simulation with Chua’s chaotic circuit verifies the effectiveness of the method.
Melanoma chondroitin sulfate proteoglycan enhances FAK and ERK activation by distinct mechanisms
Authors: Yang Jianbo , Price Matthew A. , Neudauer Cheryl L. , Wilson Christopher , Ferrone Soldano , Xia Hong , Iida Joji , Simpson Melanie A. , McCarthy James B.
Published: June 2004

Melanoma chondroitin sulfate proteoglycan (MCSP) is an early cell surface melanoma progression marker implicated in stimulating tumor cell proliferation, migration, and invasion. Focal adhesion kinase (FAK) plays a pivotal role in integrating growth factor and adhesion-related signaling pathways, facilitating cell spreading and migration. Extracellular signal–regulated kinase (ERK) 1 and 2, implicated in tumor growth and survival, has also been linked to clinical melanoma progression. We have cloned the MCSP core protein and expressed it in the MCSP-negative melanoma cell line WM1552C. Expression of MCSP enhances integrin-mediated cell spreading, FAK phosphorylation, and activation of ERK1/2. MCSP transfectants exhibit extensive MCSP-rich microspikes on adherent cells, where it also colocalizes with α4 integrin. Enhanced activation of FAK and ERK1/2 by MCSP appears to involve independent mechanisms because inhibition of FAK activation had no effect on ERK1/2 phosphorylation. These results indicate that MCSP may facilitate primary melanoma progression by enhancing the activation of key signaling pathways important for tumor invasion and growth.
The Innate Mononuclear Phagocyte Network Depletes B Lymphocytes through Fc Receptor–dependent Mechanisms during Anti-CD20 Antibody Immunotherapy
Authors: Uchida Junji , Hamaguchi Yasuhito , Oliver Julie A. , Ravetch Jeffrey V. , Poe Jonathan C. , Haas Karen M. , Tedder Thomas F.
Published: June 2004

Anti-CD20 antibody immunotherapy effectively treats non-Hodgkin's lymphoma and autoimmune disease. However, the cellular and molecular pathways for B cell depletion remain undefined because human mechanistic studies are limited. Proposed mechanisms include antibody-, effector cell–, and complement-dependent cytotoxicity, the disruption of CD20 signaling pathways, and the induction of apoptosis. To identify the mechanisms for B cell depletion in vivo, a new mouse model for anti-CD20 immunotherapy was developed using a panel of twelve mouse anti–mouse CD20 monoclonal antibodies representing all four immunoglobulin G isotypes. Anti-CD20 antibodies rapidly depleted the vast majority of circulating and tissue B cells in an isotype-restricted manner that was completely dependent on effector cell Fc receptor expression. B cell depletion used both FcγRI- and FcγRIII-dependent pathways, whereas B cells were not eliminated in FcR common γ chain–deficient mice. Monocytes were the dominant effector cells for B cell depletion, with no demonstrable role for T or natural killer cells. Although most anti-CD20 antibodies activated complement in vitro, B cell depletion was completely effective in mice with genetic deficiencies in C3, C4, or C1q complement components. That the innate monocyte network depletes B cells through FcγR-dependent pathways during anti-CD20 immunotherapy has important clinical implications for anti-CD20 and other antibody-based therapies.
Cytotoxic T Lymphocyte–based Control of Simian Immunodeficiency Virus Replication in a Preclinical AIDS Vaccine Trial
Authors: Matano Tetsuro , Kobayashi Masahiro , Igarashi Hiroko , Takeda Akiko , Nakamura Hiromi , Kano Munehide , Sugimoto Chie , Mori Kazuyasu , Iida Akihiro , Hirata Takahiro , Hasegawa Mamoru , Yuasa Takae , Miyazawa Masaaki , Takahashi Yumiko , Yasunami Michio , Kimura Akinori , O'Connor David H. , Watkins David I. , Nagai Yoshiyuki
Published: June 2004

Recently, encouraging AIDS vaccine trials in macaques have implicated cytotoxic T lymphocytes (CTLs) in the control of the simian human immunodeficiency virus SHIV89.6P that induces acute CD4+ T cell depletion. However, none of these vaccine regimens have been successful in the containment of replication of the pathogenic simian immunodeficiency viruses (SIVs) that induce chronic disease progression. Indeed, it has remained unclear if vaccine-induced CTL can control SIV replication. Here, we show evidence suggesting that vaccine-induced CTLs control SIVmac239 replication in rhesus macaques. Eight macaques vaccinated with DNA-prime/Gag-expressing Sendai virus vector boost were challenged intravenously with SIVmac239. Five of the vaccinees controlled viral replication and had undetectable plasma viremia after 5 wk of infection. CTLs from all of these five macaques rapidly selected for escape mutations in Gag, indicating that vaccine-induced CTLs successfully contained replication of the challenge virus. Interestingly, analysis of the escape variant selected in three vaccinees that share a major histocompatibility complex class I haplotype revealed that the escape variant virus was at a replicative disadvantage compared with SIVmac239. These findings suggested that the vaccine-induced CTLs had “crippled” the challenge virus. Our results indicate that vaccine induction of highly effective CTLs can result in the containment of replication of a highly pathogenic immunodeficiency virus.
THE RELATION OF DEXTROSE TO THE PRODUCTION OF TOXIN IN BOUILLON CULTURES OF THE DIPHTHERIA BACILLUS
Authors: Smith Theobald
Published: June 2004

1. Dextrose is not in itself injurious but rather favorable to toxin production. When added in quantities not exceeding 0.2 per cent to peptone bouillon freed from fermentable acid-producing substances (muscle sugar) it leads to a maximum accumulation of toxin by utilizing the available peptone to the best advantage.

2. The different courses taken by cultures of diphtheria bacilli in ordinary unfermented peptone bouillon containing muscle sugar and in peptone bouillon made from fermented infusion to which 0.1 to 0.2 per cent dextrose has been added are manifested by an increased production of toxin in the latter as well as by a rapid return from an acid to an alkaline reaction. In the former an acid reaction may prevail even under most favorable conditions.

3. These differences may be explained by assuming either that the acid products of the muscle sugar are different from those of dextrose and non-utilizable, or else that the bouillon contains certain other unknown inhibitory substances removed during fermentation. The use of synthesized media and an analysis of the acid products in fermented bouillon plus dextrose and in unfermented bouillon would aid in explaining the differences.

4. Among the accessory conditions which favor the toxin production in unfermented bouillon, as pointed out by Park and Williams, are increased quantities of peptone, well developed surface growth of the diphtheria bacilli, and a low initial acid reaction (phenolphthalein). In fermented bouillon these accessory conditions are also favoring, though of legs importance.
BACILLUS PYOCYANEUS AND ITS PIGMENTS
Authors: Jordan Edwin O.
Published: June 2004

The principal conclusions that seem to me justified are as follows:

1. The fluorescent pigment formed by some varieties of B. pyocyaneus is produced under conditions identical with those governing the production of the pigment by other "fluorescent bacteria."

2. The production of pyocyanin is not dependent upon the presence of either phosphate or sulfate in the culture medium. It is formed in non-proteid as well as in proteid media, but is not a necessary accompaniment of the metabolic activities of the organism (e. g. tartrate solution).

3. The power of producing pyocyanin under conditions of artificial cultivation is lost sooner than the fluorescigenic power.

4. There are greater natural and acquired differences in pyocyanigenic power than in fluorescigenic.

5. The fluorescent pigment may be oxidized slowly by the action of light and air as well as by reagents into a yellow pigment, and pyocyanin may be similarly oxidized into a black pigment.

6. A convenient separation of B. pyocyaneus into four varieties would be the following: var. α, pyocyanigenic and fluorescigenic (most common); var. ß, pyocyanigenic only (rare); var. γ, fluorescigenic only (not uncommon, closely related to "B. fluorescens liquefaciens"); var. δ, non-chromogenic.

7. Except for the occasional loss of one or another function the different varieties are not so plastic as sometimes assumed, and cannot be readily converted into one another by subjection to varying conditions of life.

8. The signification and correlation of the almost countless physiological variations among the members of this group in respect to growth in gelatin, behavior to temperature, indol production, etc., remain to be determined. It is not yet clear that the variations in chromogenic power can be in any way correlated with the presence or absence of other physiological functions.
THYMECTOMY IN THE RABBIT
Authors: Van Allen Chester M.
Published: June 2004

Thymectomy in the rabbit is a comparatively simple procedure. The open method described above offers many advantages over any of the closed methods and success depends largely upon the observance of a few precautions; chief among these is the avoidance of haste and the observance of aseptic technique.

The operative mortality in our series of rabbits was 10 per cent and there was an additional loss of useful animals, due to secondary complications, amounting to 16 per cent. Among the last 29 rabbits, however, there was only 1 operative death, in an old animal, and 2 cases of slight infection. It appears, therefore, that with some experience the operation can be carried out successfully in nearly all animals, especially so if comparatively young rabbits are used. Old rabbits present greater difficulties on account of the presence of dense fibrous tissue within the field of operation.

While the animals of this series showed no immediate symptoms or alteration in physical condition that could be referred to thymoprivia, it is not to be assumed that removal of the thymus is entirely without effect even on rabbits of mature age. Our observations on the reaction of thymoprivic rabbits to disease show that this is not the case and that in all probability decided effects can be demonstrated if the problem is approached on another basis. The object of the present investigation was, however, to determine whether the thymus could be completely removed from rabbits of certain ages without producing any serious disturbance of health which would interfere with their use in other experiments or complicate the interpretation of results. It was found that this could be done.
STUDIES ON THE TOXIN PRODUCTION OF THE SHIGA BACILLI
Authors: Waaler Erik
Published: June 2004

1. The S, R, and Rn variants of the Shiga bacillus are equally toxic.

2. The effect of the toxin upon rabbits is the same, whether it is derived from filtrates of broth cultures (3 to 6 days old), or is obtained by autolysis of the killed bacteria, grown on agar surface. Rabbits show in both cases prostration, loss in weight, paralysis, and diarrhea.

3. When the toxin is heated to 80°C. for 1 hour, its poisonous effect nearly disappears, but its immunizing ability is unaltered. This heated toxin induces a formation of antitoxin, which can protect against the unheated toxins.

4. The anatomical changes observed in the spinal cord (degeneration of the motor neurons) and in the cecum (hyperemia and hemorrhages) are in agreement with the statements of previous authors. Furthermore, the toxin causes hyperemia and hemorrhages in the heart, hyperemia and degeneration in the kidneys and the liver.
INFECTIOUS FIBROMA OF RABBITS
Authors: Shope Richard E.
Published: June 2004

The serial passage of Virus myxomatosum through fibroma-recovered domestic rabbits did not alter its pathogenic properties. Fully virulent Virus myxomatosumpersisted in the inoculated testicle of fibromarecovered rabbits for at least 16 days following inoculation. Virus injected into the testicles of myxoma-immune domestic rabbits, on the other hand, was promptly rendered non-demonstrable. The failure of fibroma-recovered domestic rabbits to destroy injected Virus myxomatosumand the absence from their sera of neutralizing antibodies effective against Virus myxomatosum are considered to be evidence against the identity of the fibroma and myxoma viruses. The rapidity with which fibroma-recovered rabbits develop neutralizing antibodies following infection with Virus myxomatosum is considered to be a possible factor in their acquired resistance.

It is believed on the basis of all the evidence that infectious fibroma of rabbits is a definite disease entity and not merely a mild and nonfatal form of infectious myxoma.
INHIBITION OF THE SHWARTZMAN PHENOMENON
Authors: Ogata Tomio
Published: June 2004

The Shwartzman phenomenon can be inhibited by an intravenous injection of a potent bacterial filtrate within a few hours before or after the preparatory intradermal injection.

The inhibitory effect is produced non-specifically by filtrates potent in the elicitation of the Shwartzman phenomenon, and it is of a transitory nature.

The relation of the observation described to anaphylactic desensitization and to its clinical significance is discussed in this paper.
IMMUNOLOGICAL AND CHEMICAL INVESTIGATIONS OF VACCINE VIRUS
Authors: Parker Robert F. , Rivers Thomas M.
Published: June 2004

Humoral antibodies and a certain degree of resistance to infection with vaccinia, probably not enduring, are produced in rabbits by the repeated injections of inactive formolized (0.3 per cent) elementary bodies of vaccinia and virus-free filtrates of dermal vaccine virus. Single injections of large amounts of elementary bodies are not as effective as similar amounts administered in small repeated doses. Drastic treatment (10 per cent formaldehyde or boiling for 2 hours) almost completely alters or destroys the antigenicity of elementary bodies.

It appears that the production of precipitins and agglutinins does not parallel that of neutralizing antibodies and that the mere presence of such antibodies in the serum of a rabbit as the result of injections of inactive elementary bodies does not necessarily indicate that the animal possesses a great degree of resistance to infection with a potent vaccine virus.

The fact that some neutralizing antibodies appeared in the sera of rabbits that had received injections of inactive elementary bodies can be interpreted as indicating that at least not all neutralizing antibodies for vaccine virus are the result of a reaction to an antigen produced by the host in consequence of a vaccinal infection.

No evidence was obtained to show that elementary bodies inactivated by our methods (0.3 per cent formaldehyde) would serve as a suitable vaccine for the protection of human beings against smallpox.
A CHANGE IN RABBIT FIBROMA VIRUS SUGGESTING MUTATION
Authors: Andrewes C. H.
Published: June 2004

A strain of rabbit fibroma is described causing in inoculated animals acute inflammatory lesions very different from the fibroma-like growths induced by the original strain. The new inflammatory strain cross-immunised with the normal strain but not with various other viruses. Efforts at changing one strain into the other were unsuccessful. Another, referred to as the changed, strain produced lesions of mixed character, partly inflammatory, partly fibromatous; it continued to behave in this way through numerous passages. An artificial mixture of inflammatory and fibromatous viruses behaved in all respects like the changed strain. Discussion of the significance of the findings is reserved for a separate paper (3) where the facts can be considered in relation to those described by Shope (2).
A CHANGE IN RABBIT FIBROMA VIRUS SUGGESTING MUTATION
Authors: Andrewes C. H. , Shope R. E.
Published: June 2004

A strain of rabbit fibroma virus (changed virus) producing partly fibromatous, partly inflammatory, lesions is believed to represent a mixture of the original virus with a strain (inflammatory virus) causing only necrotic and inflammatory lesions. The inflammatory virus does not represent a contamination from without, but probably arose as a mutant from the original strain. The occurrence of mutation amongst viruses and the propriety of using the word in this field are briefly discussed. Consideration is also given to the nature of the change in the virus which leads to a tissue reaction so widely different from that produced by the original strain.
ON THE GROUP SPECIFIC A SUBSTANCE IN HORSE SALIVA. II
Authors: Landsteiner K.
Published: June 2004

A method is described for the purification of the A substance in horse saliva, and additional observations on the chemical properties of the preparation are reported. The preparation isolated was found to be highly active serologically and it appears to be polysaccharide in nature.
RESPIRATORY VERSUS GASTRO-INTESTINAL INFECTION IN POLIOMYELITIS
Authors: Flexner Simon
Published: June 2004

The debated problem of gastro-intestinal versusrespiratory mode of infection in poliomyelitis has been restudied by several investigators recently, with conflicting findings. Kling and Levaditi in Europe carried out experiments from 1929 to 1933, which led them to the conclusion that the digestive tract affords a ready entrance of the virus of the disease into the body. They believe that the substitution of Macacus cynomolgus for Macacus rhesus as the animal of choice for the tests supports this point of view. Toomey in the United States has arrived at a similar conclusion, not by employing a particular species of monkey for experiment, but by the use of drastic measures of inoculation, which insure that the virus makes contact with the unmyelinated nerve fibers embedded in the intestinal wall. Toomey's methods are so severe and artificial that his results cannot be regarded as simulating a natural mode of infection.

We have repeated the tests of Kling and Levaditi, but in a far more comprehensive manner than was followed by them, and, like Clark and his associates who early repeated them, we have failed to confirm them. Indeed, we do not find Macacus cynomolgusand rhesus to differ in any essential way in their response to the presence of the virus of poliomyelitis in the body. Cynomolgido not respond to virus introduced into the stomach when contamination of the buccal and nasal cavities is avoided; they respond, as do rhesi, to virus directly injected into the intestine when virus passes into the intestinal wall and makes the necessary nerve fiber contact. Both Macacus cynomolgus and Macacus rhesus which have resisted feedings of virus are subject to nasal instillations of the same strains of virus and in the same degree.

On the basis of the experiments reported in this paper we can reaffirm the conclusion previously arrived at by ourselves, and confirmed independently by investigators in Europe and America, namely that the only established portal of entry of the virus of poliomyelitis into the central nervous system of man is the nasal membrane, and especially the olfactory nervous areas in that membrane.
STUDIES ON THE ETIOLOGY OF RABBIT POX
Authors: Pearce Louise , Rosahn Paul D. , Hu Ch'uan-K'uei
Published: June 2004

A filterable agent was isolated from 7 cases of spontaneous rabbit pox by the intratesticular injection in rabbits of a variety of tissues. The virus was transmitted for 15 consecutive testicle to testicle passages in rabbits by Berkefeld V filtrates of testicular tissue emulsions. Unfiltered emulsions were more potent than filtrates. The virulence of the virus was maintained by ice box storage of infected tissues for as long as 127 days. The pathogenic properties of the virus persisted under conditions of animal passage for the 9 months from January to October, 1933, covered by these studies.

The reaction produced in rabbits by the inoculation of tissue-virus emulsions was of two principal types, the first of which has been described and analyzed in the present paper. In the case of intratesticular injections, particularly of testicular tissue inocula, an acute fulminating and rapidly fatal condition regularly developed. The outstanding features were a massive hemorrhagic orchitis with marked scrotal edema, fever, and death within a week. The second type of reaction which is taken up in the next paper of this series (1) was observed under conditions in which the animal survived a week or longer. Occasional examples occurred in rabbits of the so called intratesticular series. The reaction was characterized by the development of a disease syndrome with a diversity of clinical manifestations which, it may be stated here for the sake of continuity, was indistinguishable from spontaneous rabbit pox.
STUDIES ON THE ETIOLOGY OF RABBIT POX
Authors: Rosahn Paul D. , Hu Ch'uan-K'uei , Pearce Louise
Published: June 2004

The clinical manifestations and course of disease observed in experimental rabbit pox have been described and analyzed. The condition differed from the acute fulminating and rapidly fatal type of experimental infection (1) in that the period of survival was longer, a variety of clinical manifestations developed and a considerable proportion of the cases recovered. The most conspicuous symptom was a generalized papular eruption on the skin and mucocutaneous borders.

The production of the disease was associated with routes of inoculation other than the intratesticular or with a small dosage. The majority of cases were inoculated with Berkefeld V filtrates of tissue-virus emulsions and not with the more potent unfiltered emulsions.

The local reactions resulting from various routes of inoculation were described. Of special interest were the pronounced cutaneous reactions induced by intradermal injection, the high instance of marked clinical manifestations after intravenous inoculation, the failure of lesions to localize in the lines of scarification of skin and cornea even in cases with a profuse cutaneous eruption, and the development of cytoplasmic inclusion bodies in the epithelial cells of the cornea following scarification and conjunctival instillation of virus.

In the character of its clinical manifestations and course of disease, experimental rabbit pox was indistinguishable from cases of the spontaneous pox.
ACTIVE IMMUNICATION OF GUINEA PIGS WITH THE VIRUS OF EQUINE ENCEPHALOMYELITIS
Authors: Olitsky Peter K. , Cox Herald R.
Published: June 2004

Active Eastern or Western equine encephalomyelitis virus in three forms,—chemically untreated but simply passaged through series of mice; adsorbed on alumina Gel C, and precipitated by tannin,—yielded practically the same results when employed for the immunization of guinea pigs.

The virus is not inactivated by the process of adsorption or precipitation : guinea pigs and mice inoculated in the brain with these materials develop lethal encephalomyelitis in the same manner as when chemically untreated mouse passage virus has been used. Moreover, there is no difference in the rate of absorption in vivoof the chemically treated and untreated virus preparations. After storage of the three immunizing preparations—the longest periods thus far studied being 2 to 3 months for mouse passage and for precipitated suspensions, and 6 months for adsorbed material—each was found to contain an amount of virus sufficient to produce immunity in animals against the usual intracerebral test inoculation. Finally, the protection afforded by the three preparations is apparently durable, as is true of many active viruses utilized in preventive treatments.

The amount of the virus necessary to confer protection may be defined as that which immunizes (a) with the least number of antigenic units and (b) with the minimum of febrile reaction and blood infection. In proportion as this amount is exceeded, the incidence of fever and of circulating virus increases and, on the other hand, as this amount is decreased, the degree of induced immunity is diminished.

We have thus shown that for this particular virus and in the guinea pig, one or two subcutaneous doses of I cc. of any of the different virus preparations, each containing 3 x 103 to 3 x 104 mouse infective units, bring about protection regularly against experimental infection by way of the nose or subcutis. The results are irregular when the test is made by way of the brain. By three injections, resistance is invariably obtained against as many as 103 to 104 lethal doses, given intracerebrally.

No matter in what form the virus is given, as mouse passage, or adsorbed, or precipitated material, in certain instances fever occurs and virus circulates. With the amount of virus adequate for immunization (3,000 to 30,000 m.i.u.) a mild or subclinical infection may occur in the guinea pig without other manifestation of disease. Lesser quantities of virus apparently fail to gain a foothold in the animal and thus fail to bring about resistance.

To conclude, a quantitative basis has been established for the comparison of the immunizing capacities of preparations employed in experimental equine encephalomyelitis in guinea pigs.
ON CROSS REACTIONS OF IMMUNE SERA TO AZOPROTEINS
Authors: Landsteiner K. , van der Scheer J.
Published: June 2004

The phenomena observed on absorption of immune sera to azoproteins with heterologous azoantigens lead to the conclusion that in general the sera do not contain a single antibody but antibody fractions somewhat different in their reactivity for heterologous antigens. From the constitution of the azocomponent it follows that these fractions cannot be specific for distinct chemical groups in the molecule. In fact, inhibition experiments showed that in the cases examined the various antibodies are all specifically directed towards the whole molecule of the homologous hapten.
STUDIES ON CULTURE STRAINS OF EUROPEAN AND MURINE TYPHUS
Authors: Nigg Clara
Published: June 2004

1. A strain of European typhus (Breinl) has been carried in cultures by means of successive transfers for a period of 1½ years, the rickettsiae in such cultures being quite as numerous as in similar cultures of murine strains of typhus.

2. The virulence of the cultures of European typhus has remained constant throughout the period of cultivation, although, on the whole, the scrotal lesions caused by the later culture generations were somewhat less marked than those produced by the first generations.

3. A strain of murine typhus has been similarly carried in cultures for 4 years with no apparent loss in pathogenicity.

4. The characteristic scrotal lesion in murine typhus in guinea pigs is apparently referable to actual predilection of this strain for the tunica tissue rather than to the number of rickettsiae injected.