bluuebunny/crossref_metadata_2025_split huggingface dataset:
INDUCTION OF BONE MARROW COLONY-STIMULATING ACTIVITY BY A FILTERABLE AGENT IN LEUKEMIC AND NORMAL MOUSE SERUM
Authors: Foster Roger , Metcalf Donald , Kirchmyer Rosemary 
Published: June 2004

1. Leukemic Swiss mice of ICR/Ha strain which had been injected at birth with a lymphoid-leukemia-inducing virus preparation yielded sera which produced elevations of serum colony-stimulating activity within 16 hr and significant plasma-LDH-enzyme elevation at 4 days when injected intraperitoneally into normal ICR/Ha Swiss mice. Colony-stimulating activity was assayed in vitro by the stimulation of hemopoietic colony formation by DBA/1 bone marrow cells.
2. The inducing agent in leukemic serum was passageable, filterable, sedimentable, and heat-, ether-, and UV-labile.
3. A similar agent was recovered from normal Swiss serum after blind serial passages through normal mice.
4. LDH elevating virus induced a similar elevation of serum colony-stimulating activity when injected at high titers, and cross-resistance was demonstrated between LDH virus and the passaged leukemic serum agent.
STUDIES ON RABBIT LYMPHOCYTES IN VITRO
Authors: Sell Stewart 
Published: June 2004

Rabbit antisera to immunoglobulin allotype Ab4 will stimulate a maximum of 77% (mean ± SEM = 39.78 ± 4.8) blast transformation of Ab4Ab4 homozygous lymphocytes in vitro and a maximum of 39% (mean ± SEM = 19.77 ± 1.6) blast transformation of heterozygous Ab4Ab5 lymphocytes. Similarly anti-Ab5 sera will induce a maximum of 82% (mean ± SEM = 50.83 ± 7.0) blast transformation of Ab5Ab5 homozygous lymphocytes in vitro and a, maximum of 42% (mean ± SEM = 16.1 ± 1.6) blast transformation of heterozygous Ab4Ab5 lymphocytes. Thus, the lymphocytes of an allotypically heterozygous rabbit appear to be selected to produce or express only one of the two genetically supplied allotypic determinants controlled by the "b" locus. A similar conclusion has been made in regard to allotypic expression by immunoglobulin-producing plasma cells.
Previous data indicate that each lymphocyte carries or expresses more than one immunoglobulin group specificity (IgG, IgA, IgM) while each plasma cell carries only one. One possible interpretation of these data is that, while the production of immunoglobulin groups and allotypic specificities are under similar control in both the lymphocyte and the plasma cell, the lymphocyte produces immunoglobulin that remains in or attached to itself and the plasma cell produces immunoglobulins that are secreted rapidly.
THE THYMUS AND RECOVERY FROM CYCLOPHOSPHAMIDE-INDUCED TOLERANCE TO SHEEP ERYTHROCYTES
Authors: Aisenberg Alan C. , Davis Caroline 
Published: June 2004

Recovery from specific immunological tolerance to sheep erythrocytes induced with the drug cyclophosphamide was studied with the hemolytic plaque technique of Jerne. The base line plaque (19S antibody-forming cell of the unstimulated spleen) and the proliferative response to antigen, both of which had disappeared during tolerance induction, returned with the recovery of specific immunological reactivity.
When cyclophosphamide is injected without sheep cells there is temporary immunological unreactivity and lymphoid depletion of the spleen, but specific tolerance is not induced. Recovery is largely complete at the end of 2 wk and does not require the participation of the thymus.
When cyclophosphamide is injected together with sheep cells, 18 days after drug injection, tolerance is still complete. In nonthymectomized mice there is rapid recovery during the next 10 wk, followed by much slower restoration over the remaining 20–30 wk of observation. The entire recovery process evidently takes 40–50 wk. In thymectomized CBA mice only minimal recovery takes place in the first 10 wk and no further restoration occurs thereafter. Thymectomy performed 18 days after tolerance is induced, when tolerance is complete, is equally effective in preventing this recovery.
ISOZYMES OF ACID PHOSPHATASE IN NORMAL AND CALMETTE-GUÉRIN BACILLUS-INDUCED RABBIT ALVEOLAR MACROPHAGES
Authors: Axline S. G. 
Published: June 2004

The acid phosphatase activity of normal alveolar and BCG-induced alveolar macrophages has been examined. Five electrophoretically distinct forms of acid phosphatase have been identified in both normal and BCG-induced macrophages. The acid phosphatases can be divided into two major categories. One category, containing four distinct forms, is readily solubilized after repeated freezing and thawing or mechanical disruption The second category, containing one form, is firmly bound to the lysosomal membrane and can be solubilized by treatment of the lysosomal fraction with Triton X-100.
The Triton-extractable acid phosphatase and the predominant aqueous soluble acid phosphatase have been shown to differ in the degree of membrane binding, in solubility, in net charge, and in molecular weight. The two pre-dominant phosphatases possess identical pH optimum and do not differ in response to enzyme inhibitors.
BCG stimulation has been shown to result in a nearly twofold increase in acid phosphatase activity. A nearly proportionate increase in the major acid phosphatase forms has been observed.
INCORPORATION OF SULFATE BY THE MOUSE THYMUS: ITS RELATION TO SECRETION BY MEDULLARY EPITHELIAL CELLS AND TO THYMIC LYMPHOPOIESIS
Authors: Clark Sam L. 
Published: June 2004

The thymus was examined in suckling mice during normal development and the involution and regeneration produced by injection of cortisol, in experiments designed to test the hypothesis that medullary epithelial cells secrete a ymphopoietic hormone responsible for controlling the magnitude of thymic lymphopoiesis. Cellular events were observed by light and electron microscopy. Lymphopoiesis was assessed, after injection of thymidine-3H, by counting the proportion of lymphocytes labeled in radioautographs of thymus. Cortical lymphopoiesis was distributed heterogeneously, being concentrated in the subcapsular region, but medullary lymphopoiesis was statistically homogeneous in distribution and similar in magnitude to the average level of cortical lymphopoiesis in suckling mice. Therefore counts of the labeling index in the medulla were used to estimate the size of the proliferating population of lymphocytes. Epithelial secretory activity was estimated by measuring the incorporation of 36sulfate by the thymus, using gel filtration chromatography to isolate soluble macromolecular 35sulfate—presumed on radioautographic evidence to represent the mucoid epithelial secretory product.
Incorporated 35sulfate accumulated rapidly for 4 hr, reached a peak at 12 hr, and had fallen to half that level by 24 hr after a single injection—as would be expected of a secretory product. During normal postnatal development the size of the proliferating population of lymphocytes and the magnitude of 35sulfate incorporation increased in parallel. During acute involution induced by cortisol both parameters diminished greatly but rose to high levels during subsequent regeneration. Accordingly, lymphopoiesis and sulfate incorporation —as defined and measured in these experiments—correlated linearly over a wide range of variation, providing circumstantial evidence to support the hypothesis that medullary epithelial cells secrete a sulfated mucoid lymphopoietic hormone. This conclusion is discussed in terms of the roles of thymus and adrenal cortex in development of the lymphoid system and maturation of immunological competence.
THE UPTAKE, STORAGE, AND INTRACELLULAR HYDROLYSIS OF CARBOHYDRATES BY MACROPHAGES
Authors: Cohn Zanvil A. , Ehrenreich Barbara A. 
Published: June 2004

The exposure of cultivated mouse macrophages to sucrose (0.009–0.03 M) leads to the formation of large phase- and electron-lucent, acid phosphatase-positive vacuoles in the perinuclear region. The vacuolization process and the uptake of sucrose-14C is blocked by inhibitors of pinocytosis and stimulated by calf serum in the medium. These results suggest the uptake of sucrose by pinocytosis and its subsequent segregation and storage in secondary lysosomes. The addition of sucrose also increases the total content of three macrophage lysosomal hydrolases.
The addition of invertase to the environment of sucrose-laden macrophages leads to the prompt shrinkage of the sucrose-containing lysosomes. This is accompanied by the intracellular hydrolysis of sucrose to fructose and glucose residues which are promptly excreted into the medium. The uptake of invertase, as indicated by the shrinkage of sucrose-containing vacuoles, is blocked by inhibitors of pinocytosis. No effect was noted when invertase was added to macrophages laden with Ficoll, a polysucrose which is not hydrolyzed by the enzyme.
The influence of other carbohydrates was then investigated. Monosaccharides with molecular weights up to 220 did not produce vacuolization. However, a certain number of di-, tri-, and tetrasaccharides produced vacuolization identical with that of sucrose. Each of the disaccharides which produced vacuolization was resistant to the complement of macrophage hexosidases, whereas those that were ineffective were degraded by either macrophage or serum enzymes. The addition of ß-glucosidase to cellobiose-laden macrophages resulted in the shrinkage of vacuoles but did not alter the vacuoles of sucrose containing cells.
The ability of small, neutral carbohydrates to produce lysosomal swelling is dependent upon both molecular weight and their resistance to lysosomal hydrolases.
THE FATE OF PEPTIDES PINOCYTOSED BY MACROPHAGES IN VITRO
Authors: Ehrenreich Barbara A. , Cohn Zanvil A. 
Published: June 2004

A series of small peptides, such as might arise in the course of intralysosomal protein digestion, were screened for the ability to escape, intact, from mouse peritoneal macrophage lysosomes. Inability to penetrate lysosomal membranes was inferred from a peptide's induction of lysosomal swelling, or vacuolization, in cultured macrophages.
Two of the peptides tested, (D-Glu)2 and (D-Ala)3, induced vacuolization. Neither peptide was susceptible to hydrolysis by enzymes in macrophages or in the serum-containing culture medium. Their morphological effect was inhibited by parafluorophenylalanine, an inhibitor of pinocytosis. Once formed by either peptide, the vacuoles persisted for several hours in peptide-free medium. Quantitative studies of radioactively labeled (D-Glu)2 confirmed the morphological evidence that (D-Glu)2 is taken up by pinocytosis and stored, intact, in macrophage lysosomes.
The majority of the peptides which failed to induce vacuolization—(L-Ala)2, L-Ser·L-Ala, L-Val·L-Ala, L-Ala·L-Thr, Gly·D, L-Phe, L-Ala·D-His, (L-Ala)3, (L-Glu)2, and D-Leu·L-Tyr—were found to be susceptible to hydrolysis by cellular or serum peptidases. Their failure to induce vacuolization was attributed to their hydrolysis to subunits capable of penetrating lysosomal membranes.
Some of the peptides which had failed to induce vacuolization—(D-Ala)2, D-Ser·D-Ala, D-Val·D-Ala, Gly-D-Asn, D-Ala·D-Thr, and D-Arg·D-Val—were found to be indigestible. Except for the cytotoxic peptide D-Arg·D-Val, peptides in this category all had lower molecular weights and volumes than (Glu)2 or (Ala)3. It is inferred that these peptides are small enough to escape from macrophage lysosomes, while (Glu)2 and (Ala)3 are too large to escape intact. The implications of this inference for the mechanism of intracellular digestion of pinocytosed proteins are discussed.
STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS
Authors: Macher Egon , Chase Merrill W. 
Published: June 2004

The fate of 14C-labeled allergens injected intradermally into guinea pigs, namely picryl chloride (PCl*) and 2:4 dinitrochlorobenzene (DNCB*), was followed during the induction period of delayed hypersensitivity. Both chemicals were applied in a single injection into one ear in amounts that approached their minimal sensitizing doses (PCl, 0.25 µg; DNCB, 5.0 µg). Radioactivity in the various tissues was determined by liquid scintillation counting after combustion of tissues to CO2 and H2O.
The injected allergens seemed to leave the injection site in three phases. A large proportion of allergen escaped rapidly from the ear, about 50% within 3 hr in the case of PCl, within 15 min for DNCB, the difference probably reflecting their unequal reaction constants. Initially there was a "half-life" escape in 2.5 hr with injected dosage of 0.25 µg PCl and in 18 hr for 5.0 µg DNCB. This escape occurred via the regional veins and not via the lymphatics. Radioactive decomposition products of the allergens were already present in the urine within 3–4 hr.
After 6–8 hr, the half-life time of escape lengthened to approximately 28 hr for both allergens used in their respective initial dosages, holding up to 2 days after which there occurred still further slowing; between 2 and 4 days the time was about 43 hr for PCl, much longer (72–88 hr?) for DNCB, apparently reflecting different physicochemical properties of this second fraction. Sensitization seemed to be connected with the portion that was present between 12 hr and 4 days of the induction period. It is not known how far the escape of radioactivity during this period may represent gradual hydrolysis of attached picryl and dinitrophenyl groupings, respectively, to form picric acid and dinitrophenol. Gradual accumulation of the second fraction in the regional lymph nodes could definitely be excluded. It was noted that no hypersensitivity arose and essentially no depot of radioactivity existed between 12 hr and 4 days when DNCB was injected in a dose of 0.25 µg, owing to its ready escape from the ear; but 20 times as much DNCB caused sensitization and provided about the same fixed depot as 0.25 µg of picryl chloride.
After delayed hypersensitivity had been established, traces of radioactivity were still measurable at the site. This third fraction, probably representing a different coupling product, escaped at a very low rate and was traceable up through several weeks.
No demonstrable radioactivity could be detected in thymus, spleen, and mesenteric nodes when examined at short intervals between ½ min and 17 days.
In analogy with findings on transplantation "immunity" and with studies reported in the following paper, the induction of delayed hypersensitivity can be explained by encounters between lymphoid cells and the hapten complex which is found present in the local site for 4 days, in agreement with Medawar's concept of peripheral sensitization.
THE HUMAN SECRETORY IMMUNOGLOBULIN SYSTEM: IMMUNOHISTOLOGICAL LOCALIZATION OF γA, SECRETORY "PIECE," AND LACTOFERRIN IN NORMAL HUMAN TISSUES
Authors: Tourville D. R. , Adler R. H. , Bienenstock J. , Tomasi T. B. 
Published: June 2004

The immunohistological localization of γA, secretory "piece" (SP), and lactoferrin (LF) in the mucosae of a variety of normal human tissues was investigated using specific fluoresceinated antisera. γA staining was localized in the apical portion of the mucosal epithelium, intercellular spaces, basement membrane area, and plasma cells of the interstitium or lamina propria of a number of normal human tissues.
SP was ubiquitous in the mucosal epithelium of all tissues studied which included parotid and submaxillary glands, bronchi, pancreas, GI tract, sweat glands, kidney, and gall bladder. In addition, SP staining was localized in the intercellular spaces and on the surface of the epithelial cells lining the lumen of the secretory glands. No SP staining was observed in the plasma cells of the interstitium or lamina propria surrounding the secretory glands in these tissues, and no SP staining was observed in sections of normal spleen or lymph node tissue. SP staining was observed in the sweat glands, pancreas, and kidney in the absence of γA staining.
LF was much less ubiquitous in the epithelial cells of the various tissues studied and appeared to be restricted primarily to the acinar epithelium of the bronchial mucosae, parotid, and submaxillary salivary glands, and was also found in renal tubular cells.
A hypothetical model for the transport of γA and SP across mucosal membrane epithelium is presented.
ESTERASES OF THE POLYMORPHONUCLEAR LEUKOCYTE CAPABLE OF HYDROLYZING ACETYL DL-PHENYL-ALANINE ß-NAPHTHYL ESTER
Authors: Becker Elmer L. , Ward Peter A. 
Published: June 2004

Previous published work has led to the hypothesis that the activatable esterase of chemotaxis is a serine esterase of the rabbit polymorphonuclear leukocyte existing in an inert, phosphonate insusceptible form, which after activation is capable of hydrolyzing aromatic amino acid esters and being inhibited by phosphonates. In the present study, directed to the testing of this hypothesis, we have shown that rabbit peritoneal polymorphonuclear leukocytes contain three esterases capable of hydrolyzing the aromatic amino acid ester, acetyl DL-phenylalanine ß-naphthyl ester. Two of these esterases, esterase 1 and esterase 2, are inhibited by various p-nitrophenyl ethyl phosphonate esters. The inhibition of each esterase is irreversible and progressive with time. When the logarithm of the esterase activity remaining after cell and inhibitor have been in contact for a constant time is plotted against the concentration of inhibitor, a straight line results. These results support the conclusion that both esterases are serine esterases. The third esterase, esterase 3, differs from the other two by its inability to be inactivated by any of the phosphonates no matter how high the concentration of phosphonate or prolonged the period of incubation of cell with phosphonate.
The activity of esterase 1 is at least 10,000 times more easily inhibited by phosphonates than is that of esterase 2; incubating rabbit polymorphonuclear leukocytes for 15 min at 27°C with 10–9–10–8 M concentrations of various phosphonates inactivates esterase 1, but it required 10–6–10–4 M concentrations of the same phosphonates to inhibit esterase 2. The inhibition profiles of esterase 1 are distinctly different from those of esterase 2 when the two esterases are tested with the phenylalkylphosphonates, chloroalkylphosphonates, and alkylphosphonates.
The inhibition profile of esterase 1 is essentially the same as that of the activatable esterase of chemotaxis obtained previously when the same three homologous series of phosphonates were tested for their ability to protect against deactivation by the chemotactic factor or give chemotactic-dependent inhibition.
It is tentatively concluded that esterase 1 of the rabbit peritoneal neutrophil is the activated form of the activatable esterase of chemotaxis.
STUDIES ON THE IMMUNOTHERAPY OF RUNT DISEASE IN RATS
Authors: Silvers Willys K. , Billingham R. E. 
Published: June 2004

Using rats of the Lewis and BN (Ag-B locus incompatible) isogenic strains, a comparative study has been made of the capacity to prevent or mitigate the development of runt disease with: (a) lymph node cell suspensions from normal adult BN rats, (b) node cells, or (c) serum from donors sensitized against Lewis tissue antigens, or (d) heterologous anti-lymphocyte serum (ALS) raised in rabbits against rat thymocytes.
Following a standard intravenous or intraperitoneal inoculation of 20 x 106 Lewis node cells into neonatal BN hosts, there are cutaneous manifestations of runt disease within 11–15 days and death invariably takes place within 20 days. However, complete protection is afforded by administration of a similar number of normal BN node cells via a different vein, or admixed with the otherwise harmful Lewis node cells. However, timing of the administration was crucially important—precedence or delay by as little as 4 hr resulted in a great impairment of protection. When the inoculations of the two cell suspensions were separated by 24 hr, no protection was afforded. These and other observations suggested that a necessary condition for protection of the hosts by unsensitized isologous cells requires that they establish a prompt and intimate confrontation with the homologous target cells.
At the same dosage level, suspensions of node cells from sensitized isologous donors were much more effective therapeutically, saving the lives of 92% of treated subjects when administered after a delay of 3 days, and of 19% when the delay was 4 or 5 days.
Of the various immunotherapeutic agents studied, daily injections of 0.2 ml of isoantiserum gave the best results, and could totally reverse the course of the disease even when initiated at age 10–13 days and subjects already presented symptoms. ALS, although inferior to isoantiserum at the dosage levels tested, proved to be superior to sensitized isologous cells as a protective agent, since the initiation of daily injections after delays of 6 or 8 days were still effective.
The observations that delayed treatments of infant rats with isoantisera or ALS resulted in complete recoveries sustain the thesis that the lesions responsible for the fatal outcome of runt diseases are not inflicted at a very early stage. The efficacy of both isoantisera and ALS as a means of inhibiting the progression of homologous disease also suggests that they may have therapeutic value in situations where this condition is encountered.
FURTHER IMPLICATION OF MURINE LEUKEMIA-LIKE VIRUS IN THE DISORDERS OF NZB MICE
Authors: Mellors Robert C. , Aoki Tadao , Huebner Robert J. 
Published: June 2004

Further evidence implicating murine leukemia-like virus in the disorders of NZB mice was afforded by a study of antigens associated with murine leukemia virus (MuLV). MuLV group antigens were prevalent in extracts of spleen, kidney, and, to a lesser extent, thymus throughout a substantial portion of the life span of NZB mice as well as in extracts of lymphomas and sarcomas indigenous to the strain.
G (Gross) soluble antigen, type-specific antigen, was first detected in plasma of untreated NZB mice at 3 months of age. G soluble antigen production increased thereafter in line with age, with 50% of reactions becoming positive at 5.3 months and 100% at 7 to 9 months.
From months 3 to 9, the time-response curve for positive conversion of direct antiglobulin (Coombs) tests in untreated NZB mice corresponded closely to that for G soluble antigen production.
Beyond the 9th month, G soluble antigen underwent elimination from the plasma of NZB mice, with positive reactions reduced to 50% at 13.3 months and to 0% at 18 months. G natural antibody was first detected in the serum of NZB mice at about 10 months of age and increased thereafter in line with age. The curves for G antibody production and G soluble antigen elimination bore a reciprocal relation to each other with crossover at 50% response occurring at 13.3 months.
Significant proteinuria, a functional manifestation of membranous glomerulonephritis, became increasingly prevalent in female NZB mice as G soluble antigen was eliminated from plasma. Cumulative mortality of female NZB mice, mainly attributable to renal glomerular disease, increased in phase with G antibody production. MuLV group antigens were identified in the glomerular lesions by the immunofluorescence method.
Positive conversion of direct antiglobulin tests was significantly delayed by vaccinating baby NZB mice with formaldehyde-inactivated cell-free filtrates of older NZB mouse spleens. The plasmas of vaccinated NZB mice with negative direct antiglobulin reactions at 4 to 7 months were likewise negative when tested for G soluble antigen. The 50% response time for G antibody production in the vaccinated NZB mice occurred at 7.3 months, that is, 6 months earlier than in untreated NZB mice.
The collective findings implicate murine leukemia-like virus in the etiology of autoimmune hemolytic disease and membranous glomerulonephritis, as well as malignant lymphoma, of NZB mice and suggest that virus-specified cell-surface and soluble antigen is a factor in the immunopathogenesis of the renal disease and possibly also the autoimmune hemolytic disease.