bluuebunny/crossref_metadata_2025 huggingface dataset:
Acquisition of cytotoxic T lymphocyte-specific carbohydrate differentiation antigens.
Authors: Lefrancois L , Puddington L , Machamer C E , Bevan M J
Published: June 2004

Cytotoxic T cell (CTL)-specific activation antigens, termed CT determinants, have been detected by monoclonal antibodies (mAb) that inhibit CTL function. At the cell surface, the CT antigens are associated with the T200 glycoproteins and two other proteins of Mr 140,000 and 85,000 and are present on a secreted protein, gp155. Periodate treatment followed by binding analysis and immunoprecipitation experiments using tunicamycin-treated cells indicated that carbohydrate is necessary for CT antigen expression. Furthermore, gp155 is secreted in the presence of tunicamycin while retaining the CT antigens, and the CT determinants are added late in T200 biosynthesis, suggesting that the CT glycans are O-linked. Finally, interleukin 2 was shown to dramatically influence the expression of the CT mAb-reactive oligosaccharides present at the CTL cell surface.
Sequential expression of antigens on sexual stages of Plasmodium falciparum accessible to transmission-blocking antibodies in the mosquito.
Authors: Vermeulen A N , Ponnudurai T , Beckers P J , Verhave J P , Smits M A , Meuwissen J H
Published: June 2004

Plasmodium falciparum gametocytes contain specific antigens, some of which (Mr 230,000, 48,000, 45,000) are expressed on the surface of the newly emerged macrogamete. A different antigen (Mr 25,000) surrounds the surface of the ookinete and, although present to some extent in the developing gametocyte, is synthesized in high quantities by the macrogamete/zygote and expressed progressively on the transforming zygote surface. These antigens are targets of transmission blocking antibodies that are effective at two distinct points after gametogenesis: fertilization of the macrogamete and ookinete to oocyst development. The antigens involved in the fertilization blockade are the Mr 48 and 45 proteins, which are expressed on the macrogamete surface. The Mr 230 K coprecipitating protein probably plays no part in transmission block. mAb directed against the Mr 25 K ookinete surface protein blocked transmission without inhibiting ookinete formation, indicating that this protein has an important role in the transformation of ookinete into oocyst. A combination of mAb recognizing different epitopes on the same protein molecule acted synergistically in inhibiting oocyst formation. Using a mixture of two blocking mAb reacting against the Mr 48/45 and 25 K proteins, respectively, an additive blocking effect could be demonstrated.
Interactions between T helper cells and dendritic cells during the rat mixed lymphocyte reaction.
Authors: Green J , Jotte R
Published: June 2004

This paper describes the interactions between dendritic cells (DC) and T helper (Th) cells in the rat mixed lymphocyte reaction (MLR). Th blasts that are actively proliferating were generated in a 5 d primary MLR; resting Th memory cells were derived from a 10-12 d MLR. The DC were purified from thoracic duct lymph derived from rats whose mesenteric lymph nodes had been removed. The results show that DC are the major stimulators in the primary MLR and also for the restimulation of Th blasts and Th memory cells. Th blasts rapidly formed large clusters when cultured with DC but not with Ia+ macrophages or B cells. This interaction was not dependent on a major histocompatibility complex (MHC) difference between the T blasts and the DC. Con A-activated T and B blasts also formed clusters when cultured with DC. Th memory cells formed small clusters with DC, but, in a different assay in which clusters are dispersed, we detected an antigen-specific interaction between Th memory cells and DC. The monoclonal antibodies W3/25 (anti-rat CD4) and MRC OX-6 (anti-MHC class II) blocked proliferation in the primary MLR and also inhibited the restimulation of Th memory cells. However, the restimulation of Th blasts in a secondary MLR was only blocked by MRC OX-6. These results suggest that there are different requirements for the restimulation of T blasts than for the activation of primary or memory Th cells. W3/25 and MRC OX-6 did not affect the clustering of T blasts with DC but they both inhibited the antigen-specific binding of Th memory cells to DC. The data suggest that the CD4 (W3/25) antigen is involved in antigen-specific interactions between Th cells and DC.
Establishment of the DU.528 human lymphohemopoietic stem cell line.
Authors: Kurtzberg J , Bigner S H , Hershfield M S
Published: June 2004

We have established the DU.528 cell line from the pretreatment leukemia cells of a patient who underwent a T lymphoblastic-to-promyelocytic phenotype conversion during treatment with the adenosine deaminase inhibitor, deoxycoformycin. The cell line and clones obtained from it by limiting dilution have the same karyotype previously found in the patient's pretreatment T lymphoblasts and post-deoxycoformycin treatment promyelocytes. DU.528 cells in continuous culture for greater than 2 yr display a predominant undifferentiated T lymphoblastoid phenotype. These cells spontaneously generate progeny of at least three lineages, T lymphoid, granulocytic/monocytic, and erythroid. The surface marker most consistently expressed by DU.528 cells in the undifferentiated state is the 3A1 antigen, which has been found on prothymocytes in the embryonic thymus. Some undifferentiated DU.528 cells also expressed the IL-2 receptor, but no other T cell differentiation antigens. Exposure of DU.528 cells to a variety of agents induced myeloid maturation; adenosine and deoxyadenosine, in the presence of deoxycoformycin, induced expression of myeloid differentiation antigens. Our results suggest that DU.528 is a lymphohematopoietic stem cell line and support the hypothesis that differentiation of pluripotent stem cells may be altered by genetic deficiency of adenosine deaminase. DU.528 cells may provide a useful model for examining factors that regulate stem cell proliferation and differentiation.
Multiple cancers. Tumor burden permits the outgrowth of other cancers.
Authors: Mullen C A , Urban J L , Van Waes C , Rowley D A , Schreiber H
Published: June 2004

We demonstrate that tumor-bearing hosts permit the outgrowth of "potentially malignant" cells that are located at a different site. These second cancers continued to grow and kill their hosts even though they retain the "premalignant" phenotype, even after removal of the original malignancy. The potentially malignant cells used in these experiments were ultraviolet light- or methylcholanthrene-induced regressor tumor cells that are rejected regularly by normal mice at any testable dose, and only form progressive tumors in immunosuppressed individuals. The immunological rejection of these highly immunogenic, potentially malignant cells was suppressed by Thy-1+, Ly-2-, nonadherent, radio-sensitive suppressor cells in the tumor-bearing mice. These suppressor cells were absent in nude tumor-bearing mice. Unlike helper and cytolytic T cell-mediated responses, which are exquisitely tumor specific, the suppression caused by a progressively growing tumor was crossreactive among many syngeneic, independently derived tumors induced by different carcinogens. However, T cell-mediated immune responses to alloantigens, allogeneic tumors, certain syngeneic tumors, and humoral responses to xenogeneic red blood cells were normal in these mice. The immune suppression in the tumor-bearing animals closely simulated that induced by ultraviolet light irradiation, and both types of suppression might therefore share common mechanisms. Our findings may contribute to understanding the growth, development, and possible control of multicentric malignancies and add a precaution to the potential use of strongly immunogenic tumor variants for active immunotherapy in hosts bearing less immunogenic tumors.
Role of membrane immunoglobulin (Ig) crosslinking in membrane Ig-mediated, major histocompatibility-restricted T cell-B cell cooperation.
Authors: Tony H P , Phillips N E , Parker D C
Published: June 2004

Resting murine B lymphocytes can present rabbit anti-Ig to T cell lines specific for normal rabbit globulin. The T cell-B cell interaction is major histocompatibility complex (MHC)-restricted, and leads to activation, proliferation, and differentiation of the resting B cell into an antibody-secreting cell. Efficient antigen presentation and B cell activation depends upon binding of rabbit globulin to (membrane) mIg. To investigate the role of mIg in this polyclonal model for a T cell-dependent primary antibody response, we determined whether crosslinking of mIg is required either for efficient antigen presentation, as measured by helper T cell activation, or for the B cell response to T cell help, since all the direct effects of anti-Ig on B cells require crosslinking of mIg. We found that monovalent Fab' fragments of anti-IgM or anti-IgD work as efficiently as their divalent counterparts. Therefore, a signal transduced through the antigen receptor seems not to be required when T cell help is provided by an MHC-restricted T helper cell recognizing antigen on the B cell surface. Moreover, rabbit globulin bound to class I MHC molecules in the form of anti-H-2K also results in efficient antigen presentation and T cell-dependent B cell activation. However, mIg still appears to be specialized for antigen presentation, since anti-Ig is presented about three- to fivefold more efficiently than anti-H-2K.
Determinants recognized by human cytotoxic T cells on a natural hybrid class I HLA molecule.
Authors: Clayberger C , Holmes N , Wang P L , Koller T D , Parham P , Krensky A M
Published: June 2004

The major histocompatibility complex class I HLA molecules are the primary determinants recognized by allogeneic cytotoxic T lymphocytes (CTL), and serve as restricting elements for CTL recognition of viral, chemical, or minor histocompatibility antigens. HLA-Aw69 is a naturally occurring hybrid class I molecule that we have used to investigate the regions of class I antigens involved in human CTL recognition. HLA-Aw69 appears to have resulted from an exon shuffle between two closely related class I genes: the alpha 1 domain of HLA-Aw69 is identical to that of HLA-Aw68, while the alpha 2 and alpha 3 domains are identical to HLA-A2. The determinants recognized by human allogeneic CTL clones specific for HLA-A2, -Aw68, and/or -Aw69 fall into three patterns: (a) CTL determinants are located on both the alpha 1 and alpha 2 domains; (b) interaction of the alpha 1 and alpha 2 domains results in new combinatorial determinants; (c) interaction of the alpha 1 and alpha 2 domains in the hybrid molecule results in the loss of CTL determinants that are present on both parental molecules. Thus, using human CTL clones, target cells, and HLA molecules, we show that the interaction of the alpha 1 and alpha 2 domains alters CTL determinants in ways not directly predictable from primary structure.
Persistent expression of Ia antigen and viral genome in visna-maedi virus-induced inflammatory cells. Possible role of lentivirus-induced interferon.
Authors: Kennedy P G , Narayan O , Ghotbi Z , Hopkins J , Gendelman H E , Clements J E
Published: June 2004

In this study we investigated the pathogenesis of the lymphoproliferative response in the chronic-active visna maedi virus-induced inflammatory lesions. Viral RNA expression was confined to macrophages, but only in tissues showing inflammatory lesions. A persistent and high level of Ia antigen expression was seen in macrophage-like cells in the inflammatory lesions, and the amounts of viral RNA and Ia expression were closely correlated. A small subpopulation of macrophages contained both viral RNA and Ia antigen, and these were found in greatest number in the lung. In vitro experiments showed that a lentivirus-induced interferon (LV-IFN) could induce Ia antigens in normal sheep spleen and lymph node cells as well as in a transformed sheep macrophage cell line. Ia antigen expression in macrophages was transient in the absence of a continuing IFN stimulus and persisted for at least 2 wk in the presence of LV-IFN. LV-IFN also restricted viral replication in macrophages. It is suggested that LV-IFN induced by the inflammatory cells in visna-maedi lesions may induce Ia antigen expression in macrophages, thereby indirectly causing the lymphoproliferative response and restricted virus replication.
Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen).
Authors: Lanier L L , Kipps T J , Phillips J H
Published: June 2004

A subset of peripheral blood T lymphocytes coexpressing CD3 and IgG Fc receptors (FcR) (CD16/Leu-11 antigen) have been identified, isolated, and functionally characterized. The CD3+, CD16+ cells were established in short-term culture using growth medium containing interleukin 2 (IL-2). Both the freshly isolated cells and the cultured cell line stably expressed the CD3+, CD16+ phenotype. Furthermore, a majority of these T cells lacked either CD4 or CD8 expression. Like in vitro-activated cytotoxic T lymphocytes and natural killer (NK) cells, the CD3+, CD16+ cells showed numerous azurophilic granules. Although these cells failed to mediate significant levels of NK cell-mediated cytotoxicity even after stimulation with IL-2, they efficiently functioned as effectors of antibody-dependent cellular cytotoxicity (ADCC). The Ig isotype specificity of the ADCC was analyzed using an isotype switch-variant family of a murine anti-HLA monoclonal antibody (mAb). Similar to the CD3-, CD16+ NK cell population, the CD3+, CD16+ T cells preferentially used the IgG2a antibody to mediate ADCC. The CD3+, CD16+ cells demonstrated a proliferative response when cocultured with either a NK-sensitive tumor cell line, K562, or a NK-insensitive B lymphoblastoid cell line, CCRF-SB. The response against CCRF-SB was significantly inhibited by anti-IL-2 receptor antibody, whereas the response against K562 was only partially diminished. Cytotoxicity was also induced in the CD3+, CD16+ population by the presence of anti-CD3 mAb, indicating that cytotoxicity can be triggered by stimulation via the CD3-T cell antigen receptor complex. By isolating these CD3+, CD16+ cells from the peripheral blood of a normal, healthy individual, it has been possible to extensively study the morphology, antigenic phenotype, and functional behavior of this unique subset of T lymphocytes expressing IgG FcR.
EFFECT OF PHOTO-OXIDATION ON ISOHEMAGGLUTINATING ANTIBODIES
Authors: Boyd William C.
Published: June 2004

Photo-oxidation (in the presence of eosin Y as a sensitizer) of isohemagglutinating sera destroyed their agglutinating activity gradually, but did not seem to convert any of the agglutinins studied into inhibiting ("incomplete" or "blocking") antibody.
PERIOD OF INFECTIVITY OF PATIENTS WITH EXPERIMENTALLY INDUCED INFECTIOUS HEPATITIS
Authors: Havens Walter P.
Published: June 2004

1. Serum and stools obtained in the pre-icteric phase of one patient, and pooled specimens of the same materials from 5 patients with experimentally induced (by feeding) infectious hepatitis produced the disease in 10 out of 15 human volunteers following feeding or parenteral inoculation.

2. Pooled specimens of urine and nasopharyngeal washings from 5 patients, obtained in the acute phase of infectious hepatitis when virus was proven to be in the stool and serum, were not demonstrably infectious when fed and given intranasally to 6 volunteers.

3. Serum obtained in the midincubation period of one patient with experimentally induced infectious hepatitis failed to produce apparent infection when inoculated parenterally into 3 human volunteers. This is in contrast to the situation in homologous serum jaundice in which "virus" has been demonstrated in the sera of volunteers during the incubation period.

4. Serum and stools obtained from one patient and pooled specimens of stools from 5 patients 25 to 31 days after onset of experimental infectious hepatitis failed to produce apparent infection in 10 human volunteers.

5. No appreciable difference was detected in length of incubation period following the parenteral administration of widely different amounts of the same strain of "virus."
THE ABSENCE OF ANTIBODY IN THE MACROPHAGES DURING MAXIMUM ANTIBODY FORMATION
Authors: Ehrich W. E. , Harris T. N. , Mertens E.
Published: June 2004

Following the injection of dysentery antigen in saline or in saline-in-paraffin-oil emulsion into the pad of the rabbit's hind foot, considerable quantities of antibody were recovered from the popliteal lymph node, while the tissue at the site of injection, containing many granulocytes and numerous macrophages, revealed only insignificant quantities of antibody.

Following the injection of various dysentery and typhoid antigen combinations into the abdominal cavity, no antibody was found in the isolated granulocytes and macrophages of the peritoneal exudate, while the supernatant fluid revealed titers that roughly paralleled those of the blood serum. Similar results were obtained when animals were injected first with antibody intravenously, and subsequently with an unspecific irritant intraperitoneally. The presence of antibody in the supernatant fluid was, therefore, interpreted as being due to secondary concentration (fixation) in an inflamed area.

These findings together with the previously described observations on the lymphocyte seem to show that the macrophage does not synthesize agglutinins against dysentery or typhoid bacilli.
THE SITE OF ANGIOTONIN DESTRUCTION
Authors: Sapirstein Leo A. , Reed Racheal K. , Page Ernest W.
Published: June 2004

1. Theoretical considerations render it unlikely that the greatest part of the angiotonase found in the organism is available for the destruction of angiotonia. A priori considerations support the view that only plasma angiotonase is involved in angiotonin destruction in vivo.

2. We have utilized the magnitude and duration of the presser response to angiotonin as an index of available angiotonase, and we have found that: (a) Nephrectomy and evisceration are without marked effect on angiotonin response. (b) Hemorrhage and hemodilution without shock cause a striking increase in the response to angiotonin and this appears to be due to removal of the plasma rather than the cells. Shock developing after hemorrhage results in a state of refractoriness to angiotonin. (c) Intact red cells in vitro have no destructive action on angiotonin, but after hemolysis they have several hundred times the activity of plasma, (d) Intravascular hemolysis, whether produced in vitro or in vivo, decreases the response to angiotonin to a degree which is consistent with the hypothesis that the normal animal destroys angiotonin entirely in its plasma. The active principle in hemolyzed blood is destroyed by heating to 65–70°C. for 15 minutes.

3. These findings support the hypothesis that all or at least the greatest part of angiotonin destruction under physiological circumstances occurs in the plasma, and the significance of this hypothesis is discussed.
IMMUNOCHEMICAL STUDIES ON BLOOD GROUPS
Authors: Bendich Aaron , Kabat Elvin A. , Bezer Ada E. ,   With an Appendix by Erwin Brand, Ph.D., and Leo J. Saidel
Published: June 2004

1. Studies on a number of individual hog stomachs have shown that substances with blood group A activity cannot be obtained from all hogs. Of ten stomachs studied, only seven yielded products with blood group A activity. All ten purified preparations, however, showed identical properties with respect to nitrogen, reducing sugar, glucosamine, acetyl, and relative viscosity. Six of the seven active samples were of equal potency in precipitating anti-A; the seventh was slightly less active.

2. Preparations from random pools of hog stomachs, although possessing the same analytical properties, were of lower activity than those from individual active stomachs as determined by the microquantitative precipitin method.

3. An immunochemical method for estimating the absolute purity of the blood group A substance by determining the proportion of its glucosamine precipitated by excess anti-A was developed. Values of about 84 per cent for the purity of six of the seven purified active preparations from the individual hog stomachs were obtained.

4. The inactive products, unlike the active ones, did not stimulate the production of anti-A on injection into human beings and did not precipitate anti-A or inhibit hemagglutination of A erythrocytes by anti-A.
THE PREPARATION OF SECTIONS OF GUINEA PIG LIVER FOR ELECTRON MICROSCOPY
Authors: Claude Albert , Fullam Ernest F.
Published: June 2004

1. A method is described whereby sections of guinea pig liver cells can be prepared for electron microscopy after fixation.

2. The high resolving powerof the electron microscope reveals the presence of two components, one particulate, the other apparently of fibrous texture, in the ground substance of the cells.
MOBILIZATION OF BASOPHILE SUBSTANCE (RIBONUCLEIC ACID) IN THE CYTOPLASM OF LIVER CELLS WITH THE PRODUCTION OF TUMORS BY BUTTER YELLOW
Authors: Opie Eugene L.
Published: June 2004

Butter yellow (dimethylaminoazobenzene) causes degenerative changes in liver cells accompanied by chromatolysis of cytoplasmic structures that stain with basic dyes because they contain ribonucleic acid. These changes are profoundly modified by the protein content of the diet.

Chromatolysis is succeeded by focal regeneration with reaccumulation of ribonucleic acid in the cytoplasm of liver cells; these foci of basophile hyperplasia have their origin in the parenchyma surrounding portal spaces and consist of cells arranged in columns or as tubules with lumina.

Hepatomas arise from foci of basophile hyperplasia and corresponding with the arrangement of cells in these foci may be trabecular or adenomatous.

Butter yellow causes new formation of bile ducts which arise chiefly in the immediate neighborhood of secondary portal spaces and produce the precancerous lesion, designated cholangiofibrosis. These bile ducts may accumulate ribonucleic acid in their cytoplasm and undergo hyperplasia.

Cholangiomas arise from newly formed bile ducts that are the site of basophile hyperplasia.

Changes accompanying chromatolysis and basophile hyperplasia aid in the definition of structural elements of the cytoplasm and in the localization of ribonucleic acid with relation to the mitochondria.
REACTIONS OF MONKEYS TO EXPERIMENTALLY INDUCED INFLUENZA VIRUS A INFECTION
Authors: Saslaw Samuel , Wilson H. E. , Doan Charles A. , Woolpert O. C. , Schwab J. L.
Published: June 2004

1. Macaca mulatta monkeys on a normal diet have proved resistant to intranasal but not to intratracheal inoculation of influenza virus.

2. Neutralizing antibodies appeared 8 to 10 days after inoculation with either living or heat-inactivated virus. The antibodies were noted to be still present as long as 9 months after infection with living virus.

3. A specific granulopenic leucopenia characteristically followed primary influenza virus inoculation, regardless of altered conditions of diet, exposure, and route of inoculation, but it was not observed in monkeys previously infected with the same virus, all of which invariably survived.

4. Nutritional deficiency and exposure to cold increased the susceptibility of monkeys on intranasal instillation of the virus; the leucopenia was profound and fatalities frequently occurred even though neutralizing humoral antibodies developed as promptly and in relatively the same titer as under optimum nutritional conditions.
PREPARATION AND PROPERTIES OF SHIGA TOXIN AND TOXOID
Authors: Dubos René J. , Geiger James W.
Published: June 2004

1. Shigella dysenteriae (Shiga) can, under the proper cultural conditions, produce a soluble toxin which is independent of the specific somatic polysaccharide antigen. A method is described for the rapid production of this toxin by an avirulent R variant of this organism.

2. The amount of bacterial protoplasm synthesized, and the yield of toxin produced, are very much increased when the culture is grown under conditions which favor aerobic metabolism and which do not permit accumulation of organic acids.

3. Although addition of an excess of inorganic iron to the medium does not interfere with the synthesis of bacterial protoplasm, maximal toxin production is obtained only in media which have been freed of the metal.

4. R Shiga bacilli grown under conditions of extreme aerobiosis at pH 7.0 in a simple medium free of inorganic iron and containing fumaric acid, glucose, meat extract, and peptone, give rise within 24 to 36 hours to cultures exhibiting a high degree of toxicity. The toxic principle rapidly becomes soluble as the cells die; it can be concentrated, purified, and freed of phosphorus by selective precipitation methods.

5. The toxin is fairly resistant to heat at pH 6.0 but rapidly denatured at pH 9.0. It is only slowly inactivated by trypsin. It filters readily and without loss of activity through anionic exchange resins but is precipitated and adsorbed by cationic resins which retain the nitrogen and toxic activity of the preparation.

6. The most active preparations of toxin available possess an LD50 of 1 to 10 µg. for mice and rabbits. Young mice (up to 5 weeks of age) are more resistant than older animals.

7. The soluble toxin can be detoxified by treatment with 0.5 per cent formalin at pH 8.5; detoxification does not take place at lower pH whereas treatment at higher pH destroys specific antigenicity. Mice immunized with Shiga toxoid (in solution, or in the form of an alum precipitate) develop active immunity to the toxin.
THE FATE OF INJECTED PARTICULATE ANTIGENS IN RELATION TO THE FORMATION OF ANTIBODIES
Authors: Harris T. N. , Ehrich W. E.
Published: June 2004

Earlier studies have shown that the injection of antigenic material into the pad of the rabbit's foot is followed by the appearance of antibodies in the regional lymph node, in lymph coming from that node, and especially in the lymphocytes present in such efferent lymph. In the present work the fate of particulate antigenic material has been investigated during the period between its injection into the foot of the rabbit and the appearance of antibodies in the regional lymphatic tissue.

It has been found that soluble substance of the same immunologic specificity as the antigenic material injected can be identified in extracts of the injected tissue and of the regional lymph node, and in the efferent lymph from that node. The concentration of this soluble material falls off slowly in the injected tissue in the course of the few days following the injection. It falls off quickly in the extract of the lymph node and in the lymph itself, and its disappearance is succeeded by the appearance of antibody.

Evidence is presented that the immunologically active substance is derived from the injected antigenic material by a physiologic process, and this process is discussed as the means by which antigens, originally comprised in cells, are made available to the lymphocyte.
EFFECT OF IN VITRO CULTIVATION ON THE PATHOGENICITY OF WEST NILE VIRUS
Authors: Koprowski Hilary , Lennette Edwin H.
Published: June 2004

The West Nile virus was cultivated in suspended cell culture media employing several different tissue components, and it has been observed to survive in culture for at least 32 days.

Continued propagation of the virus in vitro resulted in a change in its pathogenicity. The change lay in a marked reduction or a complete loss of the ability of the virus to produce fatal infections in mice and in hamsters on peripheral inoculation, although there was no obvious simultaneous alteration in the lethal effect of the virus by the cerebral route.

In mice, the extent to which invasiveness was lost depended upon the passage level of the virus and the age of the test animals. The younger (and more susceptible) the mice, the greater the number of passages which was required to diminish the virulence of the virus by peripheral routes; after 68 passages, the virus still retained its full capacity to kill 3-day-old mice, while its ability to kill 8-day-old mice was reduced and its ability to kill mice 14 or more days of age was essentially abolished. How soon the loss of pathogenicity occurs in hamsters has not been determined.

Prolonged cultivation rendered the virus avirulent for hamsters by the intraperitoneal route.
STUDIES ON THE FLEXNER GROUP OF DYSENTERY BACILLI
Authors: Perlman Ely , Goebel Walther F.
Published: June 2004

1. The toxicity of killed dysentery bacilli can be ascribed to the somatic antigen. Antibodies to intact dysentery bacilli apparently contain no toxin-neutralizing antibodies other than those which precipitate the purified somatic antigen.

2. The serological properties of dysentery bacilli are determined by the specific somatic antigen. The specificity and cross-reactivity of the somatic antigen are dependent upon the carbohydrate moiety of the molecular complex.
STUDIES ON THE MECHANISM OF RECOVERY IN PNEUMOCOCCAL PNEUMONIA
Authors: Wood W. Barry , Smith Mary Ruth , Watson Barbara
Published: June 2004

1. Evidence has been presented in previous publications that the phagocytosis of pneumococci in the pneumonic lung during chemotherapy is due neither to specific opsonins nor to capsular injury (1, 2). The present studies have shown that the phagocytosis taking place in the lung is independent of any sort of intermediary factor and results from a direct action of the phagocytic cells upon the pneumococci.

2. Phagocytosis in the absence of antibody has been demonstrated not only in the lungs of living rats but in formalin-fixed lungs, on the surfaces of a variety of tissues (both freshly removed from the animal and previously "killed" with heat), and on the surfaces of such inert materials as moistened filter paper, cloth, and fiber glass. On the other hand, smooth materials such as glass, cellophane, albumin, and paraffin have failed to support the phagocytic reaction. This latter observation indicates that the physical character of the surface to which the leucocytes have access constitutes a determining factor in the non-antibody mechanism of phagocytosis.

3. Further experiments have defined the relationship of "surface phagocytosis" to that induced by specific opsonins. The non-antibody mechanism was found to operate only upon surfaces of suitable physical properties, whereas opsonins enabled phagocytes floating freely in a fluid medium to engulf the fully encapsulated organisms.

4. Direct visualization of the surface phenomenon in the lung revealed that leucocytes phagocyte the virulent organisms in the absence of antibody only after having trapped them against the alveolar walls. Once the encapsulated pneumococci have been ingested, they can be seen to undergo digestion within a few hours.

The discovery of the phenomenon of surface phagocytosis affords clarification of previously unanswered problems concerning the mechanism of recovery in pneumococcal pneumonia.
IMMUNITY IN MUMPS
Authors: Stokes Joseph , Enders John F. , Maris Elizabeth P. , Kane Lewis W.
Published: June 2004

The results observed after experimental inoculation of active mumps virus into 41 vaccinated and 32 unvaccinated children,—with the consent of their parents or guardians,—indicated that formol-inactivated mumps virus obtained from the parotid gland of the infected monkey and employed as a vaccine in the manner which has been described increased the resistance of about half of those to whom it was administered.
CHEMICAL STUDIES ON HOST-VIRUS INTERACTIONS
Authors: Cohen Seymour S. , Anderson Thomas F.
Published: June 2004

The addition of active or irradiated T2 bacteriophage and T4 bacteriophage to E. coli B stops bacterial multiplication. The respiratory rate and respiratory quotient of the inhibited bacteria remained at the values observed just before infection. A respiratory rate decrease which occasionally appears can be roughly correlated with change of turbidity of the suspension. An intracellular inhibitor of multiplication appears to be liberated into lysates. A similar substance has been separated from normal E. coli B after sonic disintegration. These bacteriostatic preparations contain cytoplasmic granules with lactic acid dehydrogenase activity. The relationship of these phenomena to the interference effect in this system and others has been considered.
CHEMICAL STUDIES ON HOST-VIRUS INTERACTIONS
Authors: Cohen Seymour S. , Anderson Thomas F.
Published: June 2004

5-methyl tryptophane inhibited the multiplication of E. coli B without apparently affecting the rate of its oxygen utilization or R. Q. in a synthetic medium. E. coli B, under conditions of inhibition in the presence of this compound, was infected with the bacterial viruses T2 or T4. Infected organisms, in the presence of this compound, were unable to reproduce virus, assayable by the plaque method. Indeed, the number of infectious centers disappeared at a logarithmic rate in the presence of 5-methyl tryptophane, although the compound did not reduce the titers of B, T2, or T4, when the bacteria or viruses were exposed separately to the agent. In contrast to the irreversibility of the interference effects induced by viruses, the effects induced by short exposures to 5MT appear to be reversible on removal of the compound.
THE CONSTRUCTION AND OPERATION OF EXPERIMENTAL ROOMS FOR THE STUDY OF AIR-BORNE INFECTION
Authors: Robertson O. H. , Puck Theodore T. , Wise Henry
Published: June 2004

This communication describes the construction and operation of two identical experimental rooms in which it is possible to produce and maintain a wide range of temperature and humidity with or without exchange of the room air. The ability to maintain a large air mass under constant conditions makes it possible to study the effects of different atmospheric states on air-suspended bacteria and viruses in relation to their survival, particle size, humidification, killing by lethal vapors, and host susceptibility. A brief description of the functioning of the rooms under experimental conditions is given.
STUDIES ON MALARIAL PARASITES
Authors: McKee Ralph W. , Ormsbee Richard A. , Anfinsen Christian B. , Geiman Quentin M. , Ball Eric G.
Published: June 2004

1. Normal monkey, Macaca mulatta, plasma and red cells are similar in their inorganic composition to those of human beings.

Inorganic phosphate values of plasma and red cells from parasitized monkey blood are lower than normal. Plasma potassium values are higher than normal particularly during segmentation. Other inorganic components of parasitized blood show little variation from normal.

2. Monkey red blood cells parasitized with P. knowlesi consume oxygen in the presence of glucose, lactate, glycerol, and amino acids as substrates. Their respiration is inhibited by cyanide, carbon monoxide, and high oxygen tensions. Normal monkey red blood cells consume oxygen at an appreciable rate only in the presence of methylene blue.

3. Parasitized erythrocytes convert glucose to lactate at a rate 25 to 75 times that of the normal monkey erythrocyte. Unlike the normal red cell, the parasitized cell utilizes lactate if oxygen is present. Lactate is utilized, however, at a rate that is only one-sixth that of its production from glucose.

4. The significance of these findings in relation to the problem of cultivation of malarial parasites is discussed.
STUDIES ON MALARIAL PARASITES
Authors: Anfinsen Christian B. , Geiman Quentin M. , McKee Ralph W. , Ormsbee Richard A. , Ball Eric G.
Published: June 2004

1. Methods have been described for the preparation and sterilization of a synthetic nutrient medium which supports normal growth during one 24 hour asexual cycle of the erythrocytic form of P. knowlesi.

2. Successive subcultures with good multiplication can be carried out when whole blood or plasma is added to the medium. Data are presented from two such experiments where the sixth and seventh generations, respectively, were injected into normal monkeys. In both cases, the injections produced clinical malaria and in one, an abnormally severe course was observed.

3. A high percentage (95 per cent) of O2 inhibits multiplication in in vitro cultures. A gas phase approximating alveolar air permits normal development. A lower percentage (0.37 per cent) of O2 in the gas phase supports growth at least as well.

4. Certain experiments indicate that in vitro growth is better supported in normal monkey plasma than in plasma from parasitized monkeys. Heating of parasitized plasma to 56°C. for 30 minutes removed the deleterious effect.

5. A nutritional need by the parasite for glucose and p-aminobenzoic acid has been shown. Attempts to demonstrate the need for other individual components of the nutrient medium have not been successful though the effect of the absence of blocks of nutrient such as purines and pyrimidines, amino acids, or water-soluble vitamins can be observed.

6. Further assay of the nutritional requirements of the parasite appears to be hampered by the supply of nutrient furnished by the red cells and plasma. Cultivation of parasitized cells washed free of plasma and resuspended in synthetic medium containing 1 per cent serum albumin has been accomplished as one step directed toward the removal of such interfering factors.
QUANTITATIVE STUDY OF COLLAGEN CONTENT IN EXPERIMENTAL CIRRHOSIS
Authors: Morrione Thomas G.
Published: June 2004

Quantitative determinations of collagen were carried out on rat livers showing cirrhosis due to p-dimethylaminoazobenzene and carbon tetrachloride.

A twofold increase in collagen content occurred in cirrhosis due to p-dimethylaminoazobenzene. The average total hepatic collagen as well as the per cent collagen content were doubled. The collagen content after 1½ months of normal diet had fallen to normal levels.

In cirrhosis due to carbon tetrachloride, the collagen content underwent about a fourfold increase. Partial reversal with significant decrease in collagen content occurred after stopping the carbon tetrachloride. The incomplete resorption of collagen in this group can be attributed to impaired hepatic regeneration following the prolonged administration of the compound.

The chemical values for collagen parallel the quantitative evaluations of collagen content, based on microscopic examination of liver sections stained for reticulum.

Deposition of collagen in hepatic cirrhosis is not necessarily an irreversible phenomenon.
ANEMIA AND HYPOPROTEINEMIA
Authors: Miller L. L. , Robscheit-Robbins F. S. , Whipple G. H.
Published: June 2004

Dogs with sustained anemia and hypoproteinemia due to bleeding and a continuing low protein or protein-free diet with abundant iron are used to test the value of food proteins as contrasted with mixtures of pure amino acids.

The stimulus of double depletion (anemia and hypoproteinemia) drives the body to use every source of protein and all protein-building materials with the utmost conservation. Raiding of body tissue protein to produce plasma protein and hemoglobin is a factor when protein-building factors are supplied in small amounts.

In this severe test (double depletion) the good food proteins in adequate amounts are able to maintain body weight, a strongly positive nitrogen balance, and produce considerable amounts of new hemoglobin and plasma protein. Casein, lactalbumin, whole egg protein, liver protein are all adequate in amounts of 150 to 250 gm. protein per week.

Under comparable conditions mixtures of pure amino acids (essential for growth) do produce large amounts of new hemoglobin and plasma protein and a positive nitrogen balance but do not maintain body weight. The loss of weight is conspicuous even with large amounts of amino acids (200 to 300 gm. protein equivalent per week).

Methionine, threonine, and phenylalanine are related to nitrogen conservation in growth mixtures of essential amino acids (Paper I) but when these three are given together they have little influence on the doubly depleted dog (Table 3).

Some unidentified substance or compound present in certain proteins but absent in mixtures of the essential amino acids may be responsible for these differences in the response of the doubly depleted dog.
STUDIES ON THE FLEXNER GROUP OF DYSENTERY BACILLI
Authors: Goebel Walther F.
Published: June 2004

A method for detoxifying Type Z and sp. Newcastle Sh. paradysenteriae (Flexner) has been described. This procedure involves exposing the bacilli at pH 5.0 to 0.01 M periodic acid. Microorganisms treated with this reagent for an appropriate time interval lose approximately 90 per cent of their toxicity, yet they are capable of eliciting in experimental animals antibodies effective against the unaltered organisms.
FACTORS INVOLVED IN PRODUCTION OF CLOSTRIDIUM WELCHII ALPHA TOXIN
Authors: Adams Mark H. , Hendee Edelmira D. , Pappenheimer A. M.
Published: June 2004

Maximum production of the alpha toxin by Cl. welchii is dependent on the inclusion in the medium of several substances in addition to those required for growth. These factors include:

1. Some substance present in enzymatic digests of certain proteins such as casein and gelatine.

2. Glycerylphosphorylcholine and other substances that are present in extracts of pancreas.

3. The use of starch or dextrin as a carbohydrate source in the absence of other fermentable carbohydrates.

The omission of any one of these factors from the medium results in a very low yield of alpha toxin.
THE MECHANISM OF AERIAL DISINFECTION BY GLYCOLS AND OTHER CHEMICAL AGENTS
Authors: Puck Theodore T.
Published: June 2004

The effectiveness of any compound as an aerial germicide depends upon the extent of condensation of its vapor on air-suspended bacteria, and on the rate at which the resulting concentration of germicide can produce death of the microorganisms.

The properties of any compound conducive to production of the highest rate of kill of air-borne microorganisms by means of the smallest possible concentration of germicide vapor, are as folows: (a) a low vapor pressure, but not lower than 0.001 mm. Hg at 25°C.; (b) high hygroscopicity; (c) toxicity for bacterial metabolism—a high degree of potency is not necessary although the killing action will be more efficient the higher the antibacterial activity of the compound employed.

For any compound the killing action is always a direct function of the concentration of its vapor in the air. The maximum amount of a hygroscopic substance which can exist in the vapor state decreases as the relative humidity increases. Hence, at high relative humidities the bactericidal efficiency is lowest. At lower relative humidities the air can contain more vapor, and hence a greater effect is possible. At any relative humidity, the killing action is greater, the more closely the germicide vapor concentration approaches the saturation point.

The presence of soluble compounds in droplets containing bacteria promotes more extensive condensation of the germicide than would otherwise occur, and so enhances its effectiveness.

In the absence of such soluble substances, low atmospheric humidities may cause complete desiccation of a bacterial particle. Under these conditions its surface may become resistant to the condensation of the vapor, and thus prevent effective germicidal action.

The influence of temperature changes on the killing efficiency maybe correctly deduced from a consideration of the effect of a rise in temperature on the vapor pressure of the germicide and on the rate of its bactericidal action in vitro.

Equations are presented for estimating quantitatively the magnitude of some of the effects discussed.
TOLERANCE TO BACTERIAL PYROGENS
Authors: Beeson Paul B. ,   With the Technical Assistance of Elizabeth Roberts
Published: June 2004

In a study of the febrile responses of rabbits to repeated intravenous injections of pyrogenic substances from Eberthella typhosa, Serratia marcescens, and Pseudomonas aeruginosa, the following observations were made:

1. A characteristic pattern of response to daily injections of the same dose of pyrogenic material was noted. This consisted of a progressive diminution in febrile response during the 1st week or 10 days, after which an animal responded to each injection with approximately the same degree of fever, even when the injections were continued for several weeks.

2. Animals given injections of the same amount of pyrogenic material at semiweekly or weekly intervals showed some diminution in febrile reaction but the alteration was less pronounced than that in animals injected every day.

3. Pyrogen tolerance appeared to be lost quickly. Animals allowed to rest for approximately 3 weeks reacted to readministration of pyrogen with fever comparable with that which occurred after the first injection.

4. By gradually increasing the size of the daily dose of pyrogen a tolerance could be established such that a reduced, but still considerable, amount of pyrogen caused no fever whatever.

5. Rabbits that had been injected with S. marcescens or Ps. aeruginosa pyrogens showed a diminished febrile response to E. typhosa vaccine.

6. Passive transfer of the unresponsiveness to pyrogens could not be demonstrated.

7. Prevention of temperature elevations during the course of immunization by use of an antipyretic drug did not interfere with the development of tolerance to pyrogens.

8. A series of mechanically induced bouts of fever did not reduce the responsiveness to bacterial pyrogens.
ANTIPROTEINS IN HORSE SERA
Authors: Treffers Henry P. , Heidelberger Michael , Freund Jules
Published: June 2004

1. The intravenous injection of two horses with alum-precipitated rabbit serum globulin resulted in the production of antibody which gave a typical precipitin reaction without a prezone in the region of antibody excess.

2. The chemical, physical, and serological properties of this antibody are comparable to those of the more familiar anticarbohydrate antibodies.

3. The subcutaneous injection of horses with the globulin antigen gave rise to low grade "univalent" antibody which did not precipitate with soluble antigen.

4. The low grade antibody could be removed from solution by attachment to preformed specific precipitates, or by coprecipitation in the presence of "multivalent" precipitating antibody.

5. It is concluded that the familiar antitoxin type of antibody is not the only form of antiprotein response in horses but that precipitating and low grade non-precipitating antibodies may also be formed.

6. The nature of the antigen and the route of injection are demonstrated to be important factors in determining the characteristics of the antibody formed.
THE RELATIVE PRESSURES WITHIN CUTANEOUS LYMPHATIC CAPILLARIES AND THE TISSUES
Authors: McMaster Philip D.
Published: June 2004

The pressure in the cutaneous lymphatic capillaries of normal mice anesthetized with nembutal ranged between 0.0 and 2.7 cm. of water. Measurements of the interstitial pressure in the tissue immediately next the lymphatics showed that, in more than half the instances studied, there was a slight gradient of pressure from the tissues to the lymph. In nearly all the other instances the pressures inside and outside the lymphatic capillaries were approximately equal. In two cases in which lymph flow in the capillaries was rapid, the lymph pressure may have been negative. Under these circumstances there must have been a considerable gradient of pressure from the tissues to the lymph.

In skin which was rapidly becoming, or had recently become, edematous as result of the application of xylol or of heat, the intralymphatic capillary pressure generally was increased, yet when compared with the pressure prevailing in the edema fluid outside of the capillaries it was usually found to be relatively much lower, at times by as much as 5.9 cm. of water. The findings indicate that a pressure gradient is an important factor in lymph formation under normal and pathological circumstances.