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Introduction: Drusen and pigmentary abnormality are found as the hallmark to predict progression of age-related macular degeneration (AMD). In Asian populations, exudative AMD often appears in the absence of drusen but is rather accompanied by pigmentary abnormality. Recently, shallow irregular retinal pigment epithelium (RPE) elevations (SIRE) have been shown as a sign of subclinical nonexudative macular neovascularization. In this study, we aimed to investigate the characteristics of optical coherence tomography (OCT) findings including SIRE before the appearance of exudative AMD., Methods: We retrospectively reviewed 32 cases of exudative AMD that occurred in the fellow eye within the 5-year-observation period. Color fundus photography, OCT, and fluorescein/indocyanine-green angiography at the beginning of observation and at the time when exudative AMD appeared were examined to diagnose SIRE and the subtype of exudative AMD., Results: Exudative AMD was found in 19 eyes with large drusen and 13 eyes without large drusen. Mean sub-foveal choroidal thickness without large drusen was significantly thicker than that with large drusen (336 ± 109 and 220 ± 96 μm, respectively; mean ± SD). Six eyes with pachychoroid neovasculopathy, 4 eyes with type 1 macular neovascularization, and 3 eyes with PCV had occurred in the fellow eye without large drusen. Among those, 6 eyes had been accompanied by SIRE with a greatest transverse linear dimension of 1 mm or more at the beginning of observation period. Besides, small RPE elevations with a longest diameter of less than 1 mm had been observed in other 5 eyes. Three cases of polypoidal choroidal vasculopathy had originated from small RPE elevations. Moreover, pachyvessels, choriocapillaris thinning, or choroidal hyperpermeability were observed with SIRE or small RPE elevations., Conclusions: There is a non-drusen type of exudative AMD that originates from small RPE elevations as well as SIRE., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Carbon-ion radiotherapy (CIRT) for prostate cancer is both safe and efficacious; beam range calculations use relative stopping power ratio, which is derived from computed tomography (CT) values. However, hip prostheses are made of high atomic number materials and show severe artifacts on CT images. Therefore, it is not possible to accurately calculate dose distribution for CIRT in patients with prostate cancer with hip prostheses. Here, we describe the management of a 77-year-old man with prostate cancer who had previously undergone bilateral hip replacement. CIRT, in combination with androgen deprivation therapy, was recommended as definitive treatment for prostate cancer. Planning CT, magnetic resonance (MRI), and CT images with metal artifact reduction (MAR) were acquired for CIRT planning. MRI and MAR images were superimposed on the planning CT to delineate target volume and organs at risk. The radiation treatment plan consisted of a total dose of 51.6 Gy (relative biological effect) to be delivered in 12 fractions over 3 weeks, and the patient was irradiated in the supine and prone positions with a vertical beam, on alternating days. CIRT was completed as scheduled. No adverse events were observed during treatment or at 3 months after treatment initiation. While we show that CIRT may be a treatment option for patients with prostate cancer with bilateral hip prostheses, further studies are needed to evaluate treatment efficacy and late toxicity and to determine how CIRT can be administered to patients with prostate cancer with bilateral hip prostheses., Competing Interests: Hiroyuki Katoh and Daisaku Yoshida received research funding from Toshiba Energy Systems and Solutions Corporation (Kanagawa, Japan)., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

There are few reports of conversion surgery (CS) after nivolumab monotherapy because it is considered as a third-line standard chemotherapy for unresectable or recurrent gastric cancer. Here, we report a rare case of stage IV gastric cancer effectively treated with CS after nivolumab monotherapy as a third-line chemotherapy. A 73-year-old man was referred to our hospital with loss of appetite and abdominal discomfort. Stage IV gastric cancer with liver metastasis was diagnosed via upper gastrointestinal endoscopy and CT. Twelve courses of capecitabine, cisplatin, and trastuzumab were administered as the first-line treatment, 25 courses of paclitaxel plus ramucirumab as the second-line treatment, and 31 courses of nivolumab monotherapy as the third-line treatment. After 31 courses of nivolumab monotherapy, CT showed that the primary tumor shrank with no liver metastasis or ascites. Diagnostic laparoscopy was performed with no peritoneal dissemination (P0), and the peritoneal lavage cytology was negative (CY0). CS was performed with total gastrectomy and D2 lymph node dissection (R0 resection). The pathological diagnosis was U, Ant-Less, Type 2, 70 × 63 mm, poorly differentiated adenocarcinoma (ypT3N0M0 ypStage IIA). R0 resection was performed, and the histological response was grade 1a. The patient did not show recurrence for 9 months after CS., Competing Interests: None of the authors have any financial conflicts of interest to declare. All authors have confirmed that the article is not under consideration for review by any other journal., (Copyright © 2021 by S. Karger AG, Basel.)

Neonatal hypoxic-ischemic (HI) encephalopathy (HIE) remains a major cause of mortality and persistent neurological disabilities in affected individuals. At present, hypothermia is considered to be the only applicable treatment option, although growing evidence suggests that cell-based therapy might achieve better outcomes. Dedifferentiated fat (DFAT) cells are derived from mature adipocytes via a dedifferentiation strategy called ceiling culture. Their abundance and ready availability might make them an ideal therapeutic tool for the treatment of HIE. In the present study, we aimed to determine whether the outcome of HIE can be improved by DFAT cell treatment. HI injury was achieved by ligating the left common carotid artery in 7-day-old rat pups, followed by 1-h exposure to 8% O2. Subsequently, the severity of damage was assessed by diffusion-weighted magnetic resonance imaging to assign animals to equivalent groups. 24 h after hypoxia, DFAT cells were injected at 105 cells/pup into the right external jugular vein. To evaluate brain damage in the acute phase, a group of animals was sacrificed 48 h after the insult, and paraffin sections of the brain were stained to assess several acute injury markers. In the chronic phase, the behavioral outcome was measured by performing a series of behavioral tests. From the 24th day of age, the sensorimotor function was examined by evaluating the initial forepaw placement on a cylinder wall and the latency to falling from a rotarod treadmill. The cognitive function was tested with the novel object recognition (NOR) test. In vitro conditioned medium (CM) prepared from cultured DFAT cells was added at various concentrations to neuronal cell cultures, which were then exposed to oxygen-glucose deprivation (OGD). The number of cells that stained positive for the apoptosis marker active caspase-3 decreased by 73 and 52% in the hippocampus and temporal cortex areas of the brain, respectively, in the DFAT-treated pups. Similarly, the numbers of ED-1-positive cells (activated microglia) decreased by 66 and 44%, respectively, in the same areas in the DFAT-treated group. The number of cells positive for the oxidative stress marker 4-hydroxyl-2-nonenal decreased by 68 and 50% in the hippocampus and the parietal cortex areas, respectively, in the DFAT-treated group. The HI insult led to a motor deficit according to the rotarod treadmill and cylinder test, where it significantly affected the vehicle group, whereas no difference was confirmed between the DFAT and sham groups. However, the NOR test indicated no significant differences between any of the groups. DFAT treatment did not reduce the infarct volume, which was confirmed immunohistochemically. According to in vitro experiments, the cell death rates in the DFAT-CM-treated cells were significantly lower than those in the controls when DFAT-CM was added 48 h prior to OGD. The treatment effect of adding DFAT-CM 24 h prior to OGD was also significant. Our results indicate that intravenous injection with DFAT cells is effective for ameliorating HI brain injury, possibly via paracrine effects., (© 2017 S. Karger AG, Basel.)

Objective: This study was conducted to compare the differences in adipocytokines and fatty acid composition between two fraction sizes of small and large cells from subcutaneous and visceral fat of mice receiving a high-fat diet (HFD)., Methods: Body weight, blood glucose and cholesterol levels, and adipocyte diameter distribution were examined. Total adipocyte fractions could be separated into the small-cell fraction (SCF) and the large-cell fraction (LCF). Adipocytokine expression, fatty acid composition and stearoyl-CoA desaturase (SCD) expression were compared between SCF and LCF., Results: In HFD mice, body weight, glucose and cholesterol levels were significantly higher than in NCD mice. The adipocyte diameter of HFD mice continuously increased throughout the feeding period regardless of the fat depot. The expression of adipocytokine genes such as angiotensinogen, plasminogen activator inhibitor-1, adipsin, leptin, TNF-alpha and adiponectin was higher in LCF than SCF. The ratio of stearic acid to the total fatty acid content was lower in SCF than LCF, whereas oleic acid composition was higher in LCF. SCD expression was higher in LCF than SCF., Conclusion: Our results indicate that large adipocytes strongly express adipocytokine genes and show high oleic acid composition via SCD upregulation. Based on these findings, the differences in fatty acid composition between adipocyte sizes may be related to adipocytokine expression., (Copyright 2009 S. Karger AG, Basel.)

Background/aims: We established dedifferentiated fat (DFAT) cells from mature adipocytes that differentiate to multiple lineages and have characteristics similar to those of mesenchymal stem cells. In this study, we evaluated the effect of implantation of DFAT cells on habu snake venom (HSV)-induced renal dysfunction in tenascin-C knockout (TC-KO) mice., Methods: Cultured DFAT cells were incubated with PDGF-BB and immunostained with anti-desmin antibody to determine mesenchymal differentiation. HSV was injected, and DFAT cells from GFP mice were implanted in TC-KO mice via the tail vein. Expression of tenascin-C, transforming growth factor-beta(1) (TGF-beta1), and fibronectin mRNAs in the renal cortex were evaluated by RT-PCR analysis., Results: Cultured DFAT cells showed desmin immunostaining in response to PDGF-BB.HSV injection induced glomerulosclerosis, which was significantly improved by implantation of DFAT cells. Serum BUN increased after HSV injection and was significantly decreased by implantation of DFAT cells. Tenascin-C mRNA was detected in the renal cortex in implanted mice. Expression of TGF-beta1 and fibronectin mRNAs increased in the renal cortex after HSV injection, and was significantly decreased by implantation of DFAT cells., Conclusion: DFAT cells may provide a source for cell therapy for severe progressive renal disease., (Copyright 2008 S. Karger AG, Basel.)

The venous outlet of the corpus cavernosum is generally believed to be obstructed during erection. Some researchers, however, have demonstrated an increased venous outflow during erection. To elucidate this discrepancy, we carried out a pressure-flow study using a perfusion model of the penile deep artery in dogs. Various states of the corpus cavernosum, which were different in cavernous pressure, were induced by a delicate control of electrostimulation to the cavernous nerve. Inflow rate into the corpus cavernosum, inflow resistance and outflow resistance were simultaneously evaluated. The inflow rate in mild erection was higher than in the flaccid state, and the outflow rate was estimated to be also higher than in the flaccid state. A probable reason for the increased outflow rate was that the arterial resistance decreased remarkably, while the venous resistance only slightly increased. In full erection, both the inflow and outflow rates were lower than in the flaccid state because of a great venous resistance. Histological observation of the canine penis indicated that compression of draining veins passing through the tunica albuginea was weak in mild erection, while intense in full erection. It was proposed that in mild erection, the effect of venous occlusion was slight though that of arterial dilation was noticeable, resulting in an increase in the venous outflow.

Hanganutziu-Deicher (H-D) antigen is classified as a heterophile antigen and chemically defined as a glycoconjugate which contains N-glycolylneuraminic acid. H-D antigens are absent from normal human tissues, but can be expressed on a variety of human malignant cells, including melanoma. Natural anti-H-D antibodies have been detected in man with and without malignancies, but in this study when the level of antibody was compared between healthy adults and patients with melanoma, elevated anti-H-D antibody levels were found more frequently in melanoma patients for both IgM (p = 0.0001) and IgG (p = 0.0001). The present study was designed to evaluate the significance of the H-D antigen-antibody system in melanoma suppression. Sera from melanoma patients containing anti-H-D antibody reacted strongly to H-D antigen expressed on melanoma by means of flow cytometry. In a complement-dependent cytotoxicity assay this antibody killed melanoma cells in vitro. In vivo significance of the antibody was assessed by evaluating the relationship between the antibody levels and the clinical course in patients with stage II melanoma. Antibody levels were measured by enzyme-linked immunosorbent assay using a H-D glycoprotein antigen isolated from bovine erythrocytes. A significantly higher level of IgG (p = 0.0640) and IgM (p = 0.0644) anti-H-D antibody was demonstrated in those patients who were free of disease more than 5 years after surgery than in those who relapsed within 2 years. This study provides a rational basis for immunotherapy targeting H-D antigen in human melanoma.

By means of mixed agglutination test and indirect immunofluorescence test, reactions of infectious mononucleosis sera with bone marrow cells were investigated. Positive reactions were observed with bovine, murine and rat bone marrow cells, but negative results were obtained with cells of monkeys and guinea pigs. Absorption studies demonstrated that the observed reactions are due to interaction of the Paul-Bunnell antigen on bone marrow cells with its corresponding antibodies in infectious mononucleosis sera. Whereas all cells of bovine bone marrow gave positive results, only 50% of murine or rat cells were positive and these cells were shown to be neutrophilic granulocytes. Evidence was also presented that the Paul-Bunnell antigen and Fc receptor are present, apart from each other, on murine neutrophilic granulocytes.

A 22-year-old white male (L.V.) died of gram-negative septicemia complicating infectious mononucleosis (IM) that was associated with jaundice and oliguric renal failure. The kidney showed mesangial granular deposits of IgM and C3, mesangial electrondense deposits, and interstitial infiltrates of infiltrates of mononuclear cells, including atypical lymphocytes. Eluates obtained from kidney, spleen and liver contained Paul--Bunnell (PB) antibodies. Presence of PB antigens in these tissues was indicated by absorption of PB antibodies from IM sera, with the sediments resulting from tissue elutions. The IgM mesangial deposits were partially eluted with acid buffer at 56 degrees C and then reconstituted by incubation with IM sera or with immunoglobulins eluted from tissues of patient L.V. The presence in renal structures of PB antigens, IgM heterophile antibody, C3 and electron-dense deposits is consistent with the hypothesis that heterophile immune complexes were localized in the kidney and that they contribute in the pathogenisis of IM nephritis.

A pressure-flow study of the corpus cavernosum penis in the dog was performed during the flaccid, tumescent, erect and rigid stages. Perfusion was selectively made into the penile deep artery. The erect stage was induced with the local administration of papaverine hydrochloride, and the rigid stage by electrostimulation of the ischiocavernous muscle during the erect stage. Concurrently, vascular casts of the penis at each stage of erection were observed under a scanning electron microscope for the anatomical analysis of the mechanisms controlling cavernous pressure. In the pressure-flow study, it was demonstrated that a combination of decreased arterial resistance and restricted venous outflow was essential to both cause and maintain the erect state. The rigid stage was generated by contraction of the ischiocavernous muscle tightly compressing the crus penis. In the rigid stage, the cavernous pressure was elevated as high as five times the perfusion pressure; nevertheless, no backflow from the cavernous sinus to the deep artery was recognized. By use of the casts, it was confirmed that venous outflow restriction in the erect and rigid stages was due to compression of the postcavernous venules and penetrating veins in the tunica albuginea. The deep artery was occluded in the tunica albuginea in the casts made during the rigid stage, suggesting that the backflow from the corpus cavernosum penis to the deep artery was prevented by this occlusion. Therefore, in the rigid stage, the arterial and venous occlusion isolated the cavernous sinus from the systemic circulation; this mechanism seems to account for the maintenance of the extremely high cavernous pressure.

Dextran and antidextran antibodies were examined by enzyme immunoassay (EIA) and immunodiffusion in sera of 108 patients with various liver diseases. In EIA, IgG class antidextran antibody was detected in 16 patients (14.8%), mostly with chronic liver diseases such as liver cirrhosis (26.9%) and chronic hepatitis (22.2%). IgM class antibody was detected in 10 patients (9.2%). Results obtained by EIA inhibition revealed that dextran antigen was present mostly in sera of patients with acute liver diseases such as fulminant hepatitis (75.0%) and acute hepatitis (17.2%). Identity of the dextran antigen in the liver diseases serum and the dextran preparation recognized by an antibody-containing serum was demonstrated. These results suggest that the damaged hepatocytes in the process of the liver disease may release the dextran antigen into the patient's circulation which is responsible for the formation of antidextran antibodies by the patients with liver diseases.

Sera of patients with infectious mononucleosis (IM) and various other diseases were studied for agglutinins against Newcastle disease virus (NDV)-modified human group O red blood cells (NDVO) and antibodies to the NDV preparations. In agreement with previous studies, the NDVO antibodies are found in a wide variety of diseases in addition to IM, including Japanese IM-like syndrome (22%), syphilis (24%), lepromatous leprosy (30%), systemic lupus erythematosus (29%), multiple sclerosis (18%) and cancer (17%); these antibodies were also found in patients with renal allografts (29%). It was also noted that the Victoria (VIC), Roakin and Herts strains, but not B1 strain of NDV are active in the NDVO agglutination, and VIC and Roakin strains, but not B1 strain in the immunodiffusion. Immunodiffusion and enzyme immunoassay with various preparations of the VIC strain revealed that the major antigen(s) of the virus under study is carried by the hemagglutinin-neuraminidase (H-N) glycoproteins. The H-N molecule was also shown to be able to modify human erythrocytes for the agglutination by the pathologic sera.

Gangliosides were purified from melanoma tissue extracts obtained from 5 patients. GM3 and GD3 were identified as the major components in ganglioside fractions of the melanoma tissues. Following thin-layer chromatography, enzyme immunostaining with Hanganutziu-Deicher (H-D) antigen-specific chicken antisera demonstrated the presence of NeuGc-neolactotetraosylceramide (H-D5) and NeuGc-lacto-N-norhexa-osylceramide (H-D7) in all 5 melanoma extracts.

Sera of patients with various liver diseases were examined for the presence of Hanganutziu-Deicher (H-D) antibodies by enzyme immunoassay with high-molecular weight glycoprotein (HMWGP) isolated from bovine red blood cell stromata. IgG class H-D antibodies were demonstrated in sera of 5.9% of acute hepatitis, 28.1% of chronic hepatitis and 21.9% of liver cirrhosis patients. H-D specificity of the antibodies under investigation was determined by absorption experiments. Evidence was also presented that the H-D antibodies in the liver disease sera are directed to N-glycolyl neuraminic acid (NGNA) and/or NGNA-dependent determinants of HMWGP.

Sera of patients with lepromatous leprosy were studied for the presence of a variety of antibodies and immune complexes (IC). The frequencies of heterophile, Hanganutziu-Deicher and Forssman antibodies were 61 and 43%, respectively, which were significantly higher than those in other diseases. The frequency of antibodies to cardiolipin was 89% and the frequency of rheumatoid factor was 34%. Circulating IC were demonstrated in 54% of the patients' sera by Raji-cell test and in 43% by anti-antibody inhibition test. Analyses of immunoglobulin classes of IC revealed that IgG was predominant in IC of patients with lepra reaction (LR) and IgM in patients without LR. Immune deposits were found in and between cells of dermis in skin biopsy specimens of patients with LR.

By means of mixed agglutination test with staphylococcal protein A indicator system, DRw antigens were studied on lymphocytes obtained from tonsils, peripheral blood and thymuses. Monospecific antisera to DRw 1, 2, 3, 6 and 7 which were preadsorbed with pooled platelets gave mixed agglutination titers of 300 or more against B cells of human tonsilar lymphocytes and peripheral blood lymphocytes. The DR phenotypes of human tonsilar lymphocytes and peripheral blood lymphocytes determined by mixed agglutination tests corresponded to those established by lymphocytotoxicity tests. Upon stimulation of thymocytes or T cells of peripheral blood lymphocytes by Con-A, DRw antigens became detectable by mixed agglutination tests. Simultaneous experiments on the stimulated T cells of peripheral blood lymphocytes by membrane fluorescence tests showed that 21-45% of the stimulated T cells possessed DRw antigens at a detectable level, while less than 2% of unstimulated cells were positive. These results indicated that DRw antigens are present in the subpopulation of T cells which may expand in the response to Con-A stimulation.

Expression of heterophile antigens was studied on 6 human melanoma cell lines. Paul-Bunnell and Hanganutziu-Deicher (H-D) antigens, but not Forssman antigen, were demonstrated on these cell lines. H-D antigen was also demonstrated on melanoma cells isolated from primary and metastatic lesions. Evidence was also presented that HLA class I but not class II (DR and DQ) molecules are expressed on these cell lines. H-D antibodies of IgG class were detected in 10 of 23 (42%) melanoma patients suggesting the possibility that H-D antigen might have been expressed in an immunogenic form in the patients.

Sera of 6 patients with Chediak-Higashi syndrome and sera of their mothers were studied for heterophile antibodies. Sera of 5 patients as well as 5 sera of their mothers contained antibodies against trypsinized bovine erythrocytes, tissue sediments of guinea pig kidney or high molecular weight glycoprotein (HMWGP) of bovine erythrocyte stromata. The antibodies combining with HMWGP in enzyme immunoassay belonged to IgM and IgG classes. Although none of the sera had significant titer of agglutinins against sheep erythrocytes, on the basis of absorption and inhibition studies, these antibodies seemed to belong to the Hanganutziu-Deicher group of antibodies.

HLA specificity of alloantibodies involved in antibody-dependent cell-mediated cytotoxicity (ADCC) was investigated using PHA-induced lymphoblasts ( PLB ) from peripheral blood and Epstein-Barr virus-induced human lymphoblastoid cell lines (LCL). The ADCC activity with PLB sensitized by HLA-A or HLA-B antibodies was relatively low, but higher than that of control. DR antibodies completely failed to sensitize PLB for ADCC. LCL sensitized by corresponding DR antibodies gave strong ADCC reactions, independent from their D phenotypes. The ADCC reactions against LCL were abolished by absorption of the DR antibodies from the alloantisera. Thus the ADCC with LCL would provide a procedure to study the role of DR antibodies in chronic rejection of long-term renal allografts.

The multiple nature of heterophile, Paul-Bunnel (P-B) antigen has been suggested by our previous studies as well as those of others. In the present study, two distinct antigens of P-B specificity were defined by means of hemagglutination and immunodiffusion tests in agarose gel; one antigen (BS) was shared by bovine (BRBC) and sheep red blood cells (SRBC) and another antigen (B) was limited to BRBC. Both anti-BS and anti-B antibodies were shown to be present in sera of 106 patients with infectious mono-nucleosis (IM) whereas they were virtually absent from the sera of the vast majority of patients with diseases other than IM and normal sera. Absorption and agglutination inhibition tests demonstrated the presence of BS and B antigens on horse erythrocytes. Goat erythrocytes were also shown to possess BS antigen, however, B antigen was found on erythrocytes of some but not all individual goats. By means of the previously established procedure, BS antigen was extracted from stromata of BRBC, SRBC and erythrocytes of horse and goat, and B antigen from BRBC and erythrocytes of some goats. BS and B antigens were also extracted from bovine lymphocytes and murine thymus and spleen tissues but not murine erythrocytes.

Specificity of antibodies to Victoria strain of Newcastle disease virus (NDV) found in infectious mononucleosis (IM) and other pathologic sera was investigated by agglutination of NDV-modified human O red blood cells, as well as by immunodiffusion and enzyme immunoassay with various preparations of the virus. These studies clearly demonstrated that the NDV antibodies are distinct from P-B or H-D antibodies. The unexpected observation that guinea pig kidney (GPK) tissues absorbed NDV antibodies allowed their classification into a group of 'GPK-positive' heterophile antibodies. The simultaneous occurrence of the NDV antibodies and H-D antibodies in IM and other diseases suggests the possibility that multiple new antigenic determinants, especially those of carbohydrate nature, may appear due to the alteration of self-antigens as a result of various pathologic processes.

Mixed passive hemagglutination (MPHA) test was established using platelet-supernatant and indicator cells coated with purified antihuman IgG antibodies. The supernatant was shown to contain HLA A and B antigens, platelet alloantigens and blood group A, B and H antigens released spontaneously from the platelets. Unlike the MPHA with platelet monolayer, the in vitro-formed immune complex (IC) or IC containing pathologic sera did not give positive reactions in the MPHA with platelet supernatants presumably due to relatively low Fc receptor activities of the supernatants. By means of this test, HLA A or B antibodies were demonstrated in sera of 32 (44%) of 72 patients with multiple platelet transfusions including 'cytotoxicity negative absorption positive' sera. This test would provide a sensitive procedure for cross-match of sera of recipients of platelet transfusion and screening of HLA A and B typing sera.

Treatment of splenocytes and lymph node cells of 5 month-old MRL/lpr mice with TPA induced IL-2-dependent proliferation of the cells in the presence of CA++. The induced response was inhibited completely by a monoclonal antibody to IL-2 receptor. The combination of TPA and A23187 in the lpr cells induced both proliferation and production of IL-2 in a Ca++-dependent fashion. The proliferative response of the lpr cells was equivalent to that of congenic (MRL/+/+) or normal cells, but the quantity of IL-2 secreted from the lpr cells was significantly less than that of the controls. Actinomycin D, but not mitomycin C, blocked IL-2 secretion from the treated lpr cells indicating de novo synthesis of IL-2 mRNA in the cells. Thus the lpr lymphocytes can be activated to proliferate in response to IL-2, yet they do not secrete IL-2 at a normal level even if activation signals are transmitted into the cells.

Double diffusion tests in gel were employed for studies of reactions between infectious mononucleosis sera and extracts of bovine, sheep and equine erythrocyte stromata. The extracts were obtained by ultrasonication of stromata prepared from trypsin-digested erythrocytes. The reaction with bovine stroma extract was composed, in many instances, of two lines. A single line was observed in reactions with sheep and equine stroma extracts. This line merged into a reaction of partial or complete identy with one of the lines formed with bovine stroma extract. Evidence was obtained that some infectioous mononucleosis sera may contain heterophile (Paul-Bunnell) antibodies belonging to IgG class in addition to those of IgM nature.

By means of killing and/or FACS sorting the double-negative (DN) Lyt2-, L3T4- cells, Lyt2+ or L3T4+ cells and B220- cell populations were separated from T-cell-enriched lymph node (LN) cells of 4- to 5-month-old MRL/Mp-lpr/lpr mice. These highly purified cell populations were examined for their proliferative responses, interleukin 2 (IL2) production and expression of IL2 receptor (IL2R) in response to phorbol myristate acetate (PMA) and the calcium ionophore A23187 (A2) or PMA plus concanavalin A. The DNT-cell population was unable to respond to the stimuli and did not express IL2R. Thus the DN T cells, the major population responsible for the lymphadenopathy, possess fundamental defects in signal transduction as well as in the IL2-IL2R-mediated function. On the other hand, Lyt2+ or L3T4+ T cells obtained by sorting or B220- cells purified by the sorting after killing B220+ cells, exhibited proliferative responses indistinguishable from that of LN cells of the congenic MRL/Mp-+/+(+/+) mice. These cells also expressed IL2R after stimulation, however, the amount of IL2 produced was significantly lower than that produced by congenic +/+ cells. This suggested that phenotypically normal Lyt2+ or L3T4+ T cells of lpr LNs also possess a partial defect in the signal transduction system for IL2 production under the influence of the lpr gene.

By means of double-diffusion precipitation tests in agarose gel with selected infectious mononucleosis (IM) sera, an antigen was detected in sera of patients with syphilis and leprosy. Of 378 syphilis sera tested 39 (10.3%) and of 36 leprosy sera 7 (19.4%) gave positive results. Sera of patients with various other diseases were negative. This antigen was demonstrable in sera of patients with both early and late syphilis and was shown to be unrelated to cardiolipin. Absorption studies of the IM sera with bovine and sheep erythrocytes and guinea pig tissues revealed that this antigen was identical with or closely related to the previously described B antigen of the Paul-Bunnel (P-B) antigenic complex and distinct from heterophile antigens of Hanganutziu-Deicher (H-D) and of Forssman specificity. However, 2 of 89 syphilis sera without the P-B antigen were shown to contain antigen(s) of H-D specificity. None of the syphilis or the leprosy sera contained P-B antibodies, but H-D antibodies were found in 13% of syphilis sera.

A classification of heterophile antibodies is proposed, which is based on interactions with guinea pig kidney homogenate. The major groups of antibodies combining with guinea pig kidney encompass Hanganutziu-Deicher antibodies, Forssman antibodies, and antibodies to Newcastle disease virus. Antibodies which fail to combine with guinea pig kidney are primarily those of Paul-Bunnell variety.

The described test of inhibition of AA activity proved to be a procedure of exquisite sensitivity and specificity for detection of immune complexes. This could have been expected since AA is an antibody specifically combining with IgG antibody that suffered molecular transformation in the reaction with its corresponding antigen. Complexes formed at or close to the equivalence zone were most active in inhibiting AA, whereas those at extreme antigen excess did not inhibit it at all. Inhibition of AA was capable of detecting circulating immune complexes as well as immune complexes deposited in the tissues. It was also shown that by using this procedure, identification of the antigen participating in immune complex formation is feasible since excess of the specific antigen converts inhibitory complexes into inactive complexes.

By means of agglutination inhibition test, Paul-Bunnell (P-B) antigen was demonstrated in sera of patients with cancer (5%), lymphomas or leukemias (12.5%) and rheumatoid arthritis (RA) (1.4%) as well as in synovial fluids from RA patients (27%). In contrast, none of 124 normal human sera gave positive results. P-B antigen was also demonstrated in 3 of 12 perchloric acid extracts of cancer tissues and 2 of 11 saline extracts obtained at 100 degrees C from spleens of lymphoma-leukemia patients. Extracts of apparently normal tissues from 16 individuals gave negative results.