Paul H. Black's research while affiliated with University of Massachusetts Boston and other places

Publications (180)

Article
Previous studies from this laboratory had shown that exposure of mice to cold water stress leads to an increase in the secretion of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF alpha) from their peritoneal macrophages. We now report that the secretion of IL-6 from peritoneal macrophages is also increased after cold water stress and tha...
Article
We have recently shown that substance P (SP) participates in the stress-induced modulation of elicited, peritoneal macrophage function. This study reports the in vitro effects of SP on macrophage activity. We show by an MTT bioassay that SP significantly increases cellular metabolic activity. We show by ELISA that preincubating (priming) the macrop...
Article
The present paper further links nervous-endocrine-immune systems by describing influences of SP on the immune system, and more specifically, on macrophage function. We have discussed how macrophages are important to immune responses in that much of cellular and humoral responses depend on macrophage function. Macrophages are sensitive to stress in...
Article
Recently, it has been shown that intra- and extracellular thiol levels are significantly lower than normal even in the relatively early stages of human immunodeficiency virus (HIV) infection. It is plausible that this deficiency could contribute both to the loss of T-cell function and the ability to replenish T cells associated with HIV infection....
Article
Thirty depressed psychiatric inpatients, including 18 with a diagnosis of major depression, and 25 hospital staff controls were compared with respect to cellular immune function--that is, mitogen responsiveness to concanavalin A (con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM); natural killer cell (NK) activity; and T cell subsets, inc...
Article
A number of studies indicate that stress can result in suppression of the immune system in animals and man. Most of the studies have focused on alterations of lymphocyte function while only a few have investigated alterations of macrophage function or macrophage cytokine production. Macrophages play an essential role in homeostasis of the immune re...
Article
This investigation examined the effect of retinoic acid on tumor progression and immunological status of mice bearing the B16-F10 melanoma (previously selected for high lungcolonizing capacity). Tumor cells were implanted s. c. in syngeneic C57BL/6 mice, half of which were treated with β-all trans retinoic acid (RA). Although RA failed to exhibit d...
Article
Differentiation of the human teratocarcinoma derived cell line. PA-1, with retinoids was examined at concentrations (10(-6)-10(-8) M) that did not exhibit an antiproliferative effect during log-phase growth. Treatment with naturally occurring retinoic acid or certain synthetic retinoids (13-cis retinoic acid, Ro10-9359, and Ro13-7410), while not si...
Article
Treatment of AIDS patients with zidovudine is associated with an increase in lymphocyte counts. The mechanism for this increase is unclear and somewhat surprising in view of the myelosuppressive effect of zidovudine. To investigate this further, we measured lymphocyte numbers, T-cell subsets, and the ability of peripheral blood mononuclear cells (P...
Article
One contributing factor to the loss of T cells in AIDS may be the impaired ability of T cell precursors to expand, as reflected in a decreased ability of patient cells to form T cell colonies in agar. We and others have noted such a defect in people with AIDS and ARC, and have found that suppressor cells and suppressive plasma contribute to decreas...
Article
A group of men with AIDS who chose to follow a macrobiotic regimen as an alternative form of therapy was studied for the possible influence of psychological factors on their clinical progression. In this group, men with Kaposi's sarcoma (KS) had an estimated survival time of 60% at 3 years. Moreover, there was a tendency for lymphocyte number to in...
Article
Tumor cells release intact portions of their plasma membranes in the process of membrane fragment shedding. This released material has been shown to inhibit various synthetic functions of normal cells, which may play an important role in certain patho-physiological events occurring in advanced-stage cancer patients. Our studies on metastatic varian...
Article
We have considered factors that predispose to infection by the human immunodeficiency virus as well as the clinical consequences of infection. We have also reviewed what is known about the virological status of the asymptomatic carrier, particularly the female, and the fact that pregnancy may be a cofactor for progression of HIV disease in seroposi...
Article
A decline in T-cell lymphocyte number is the central characteristic of acquired immune deficiency syndrome (AIDS). The reason for the loss of these cells is not well understood. We investigated the hypothesis that defects in T-cell differentiation contributed to T-cell loss using an in vitro colony assay that measures T-cell precursor (CFU-T) frequ...
Article
Immunosuppression is frequently observed after traumatic injury, and is associated with the subsequent development of sepsis. Although a number of factors such as age, nutritional status, and the degree of injury have been related to the severity of the immunosuppression that occurs, the physiologic alterations leading to immunosuppression are not...
Article
Immunosuppression is frequently observed after traumatic injury, and is associated with the subsequent development of sepsis. Although a number of factors such as age, nutritional status, and the degree of injury have been related to the severity of the immunosuppression that occurs, the physiologic alterations leading to immunosuppression are not...
Article
The phenomenon of shedding of cell surface macromolecules and their importance in the cancer process has been reviewed with particular emphasis on tumor membrane fragments. With cell activation (during growth or stimulation of normal cells), there is an increase in synthesis, processing, insertion, and eventual, intact release of certain membrane p...
Article
Two timely and important articles in this issue of the Journal deal with infection of the central nervous system by the human T-cell lymphotropic virus Type III (HTLV-III). The article by Ho et al.1 indicates that acute infection of the central nervous system occurs with seroconversion to the HTLV-III agent. This study further indicates that certai...
Article
The macrophage plasma membrane is a major site of the cell's activities, including phagocytosis, antibody-dependent cellular cytotoxicity, and antigen presentation. To present antigen, the expression by the macrophage of immune region-associated (Ia) antigen is required. The turnover and fate of this cell surface constituent was studied in macropha...
Article
Shed plasma membrane-derived vesicles from metastatic variants of the murine B16 melanoma were examined for their ability to inhibit the induction of murine immune region-associated (Ia) antigen expression on macrophages, the initial step in the formation of an immune response. Membrane material that appears as a greater than 50 million-dalton frac...
Article
The expression of immune region-associated (Ia) antigens by macrophages is a prerequisite for antigen presentation, which is necessary for the activation of T helper cell function. A decrease in macrophage Ia expression is associated with a decrease in immune function in vitro. However, the effect of diseases accompanied by immunosuppression, such...
Article
We previously demonstrated that membrane vesicles shed by the F10 variant of the murine B16 melanoma cell line inhibited the induction by interferon-gamma (IFN) of murine macrophage immune response region-associated (Ia) antigen expression. In this paper we present evidence that the inhibition of macrophage Ia antigen expression is a selective effe...
Article
Head injury and multiple trauma patients were evaluated for mitogen responsiveness and lymphocyte subset frequencies within the first few days after injury. The profile obtained was compared to the patient's clinical course to see if there was a relation between early immune abnormalities and the subsequent development of unanticipated sepsis. Lymp...
Article
Although infection with HTLV of a minority of patients with AIDS or patients with pre-AIDS or both apparently occurs, it is unlikely to be in itself the cause of AIDS. Certainly, there may be more than one cause of AIDS and the factor (or factors) inducing the immunosuppression may not be the same as the factor (or factors) causing the neoplasia.
Article
The various manipulations involved in the isolation of membrane fragments from culture fluids of murine melanoma cells were examined to discern their effect on membrane fragment structure. Ultracentrifugation and gel chromatography were compared using the presence of marker enzymes and the sensitivity to a non-ionic detergent (Triton X-100). Fracti...
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Full-text available
Short exposure of cultured quiescent cells to micromolar quantities of beta-all-trans-retinoic acid (RA) has been reported to potentiate the effects of phorbol myristate acetate in promoting the transition from the resting to growing states of these cells. Longer periods of exposure to RA result in substantial inhibition of cellular proliferation....
Article
Full-text available
All-trans-beta-retinoic acid (RA) has both comitogenic and antiproliferative effects on murine Swiss 3T3 cells. Treatment of quiescent 3T3 cells for less than 24 hr with micromolar concentrations of RA potentiates subsequent mitogenic response of those cells to phorbol 12-myristate 13-acetate. Longer exposures of 3T3 cells to RA result in inhibitio...
Article
Exposure of Swiss 3T3 cells to micromolar quantities of beta-all-trans-retinoic acid (RA) results in either inhibition of growth or stimulation of cellular responsiveness to mitogens, depending on the length of treatment. Inhibition of growth is produced by treatment of the cells with RA for at least 48 hours. The total cellular pools of adenosine...
Article
Full-text available
Hybridoma cell lines secreting monoclonal antibodies to carcinoembryonic antigen (CEA) were generated by fusing mouse immune lymphocytes with the mouse myeloma variant cell line, NS-1. Antibody secreted by one cloned hybrid cell line could bind only a select portion of the CEA bound by the commercially available goat anti-CEA antiserum used in clin...
Article
The tumor promoter, phorbol myristate acetate (PMA), stimulates plasminogen activator production and extracellular release in confluent Swiss 3T3 cells. Coordinated with the increased extracellular release is a redistribution of the activity into plasma membrane-enriched fractions and a shift in the predominant molecular weight species from 75,000...
Article
In quiescent cultures of 3T3 cells, plasminogen activator (PA) is found predominantly as a 75,000 dalton species. When quiescent cells are exposed to mitogenic agents such as phorbol myristate acetate, Ca++, or 25% serum, the absolute levels of PA in cell lysates may either increase or decrease. However, a consistent observation is that in the stim...
Article
Treatment of confluent Swiss 3T3 cells in serum-free medium with colchicine, a drug known to depolymerize microtubules, results in a dose-dependent increase in both released and cell-associated plasminogen activator levels. Other anti-microtubule drugs (vinblastine and nocodazole) are also active in stimulating plasminogen activator expression. In...
Article
Treatment of human embryonic lung cells with dexamethasone resulted in a decrease in plasminogen activator activity measured in the fibrinolytic assay. The decrease in activity could at least partially be explained by the presence of an inhibitory substance(s) based on the following observations of lysates of dexamethasone-treated vs. control cells...
Article
This chapter describes a method for assaying the effect of interferon on plasminogen activator (PA) using, as an example, simian virus 40-transformed Swiss mouse 3T3 (SV3T3) cells treated with mouse L-cell interferon. The experience with this model is useful to others for working with different cell types or interferon sources. Plasminogen activato...
Article
The release of products from cells is commonly called secretion. Secretion implies the release of the soluble contents of secretory vesicles by a process known as exocytosis. In recent years, however, it has become clear that exported products may be cell-surface molecules that are shed from cells. Shedding implies the release in soluble or particu...
Article
Treatment of simian virus 40-transformed 3T3 cells with 1 microM beta-all-trans-retinoic acid (RA) resulted in a 5- to 6-fold enhancement of plasminogen activator (PA) release. Intracellular PA levels rose to twice control levels. Confluent 3T3 cells were less responsive to RA. In 6 of 10 experiments, no increase in 3T3 cell PA levels was noted, al...
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Full-text available
The selective removal of nonviable cells from suspension cultures of lymphoid cell lines by buoyant density centrifugation at 400 x g on a Ficoll-Hypaque (FH) cushion is described. Viable cells collect at the medium-FH interface whereas nonviable cells pellet. This method has proven useful in separating viable from nonviable cells with human lympho...
Article
We studied Epstein-Barr (EB) virus excretion and antibody in 41 renal transplant recipients enrolled in a placebo-controlled trial of human leukocyte interferon. Half the patients were also treated with antithymocyte globulin. Epstein-Barr virus excretion occurred more often in recipients of cadaver kidneys (P = 0.03) and those receiving antithymoc...
Article
To investigate the possibility that DNA damage and/or inadequate repair of such damage may be involved in the development of disease in NZB mice, the authors compared the ultraviolet light (UV) sensitivities of three NZB mouse cell lines with those of several other murine cell lines. It appears that recovery from ultraviolet light damage is consist...
Article
Production and release of high levels of plasminogen activator, a serine protease often referred to as a secretory product, has been considered as a biochemical index for mouse macrophage “activation”. Although the mechanism for plasminogen activator release is not known, several characteristics of the release process suggest that the enzyme may be...
Article
During acute cytomegaloviral (CMV) mononucleosis, mononuclear leukocytes displayed diminished responsiveness to certain mitogens. Responses to phytohemagglutinin were normal in patients with community-acquired CMVillness but were reduced in patients with transfusion-associated infection. Both groups were hyporesponsive to pokeweed mitogen and conca...
Article
The induction of virus synthesis and sister chromatid exchange (SCE) formation was investigated in several mammalian cell lines. Ultraviolet light co-induced the production of virus and SCEs in Simian virus 40 (SV40) transformed hamster cells. Post-irradiation treatment with caffeine enhanced virus induction, though it caused a smaller, less consis...
Article
The reactivation of UV-irradiated herpes simplex virus (HSV) was investigated in irradiated and unirradiated transformed hamster cells in which infectious simian virus 40 (SV40) can be induced. Reactivation was enhanced when the cells were treated with UV light or mitomycin C prior to infection with HSV. The IV dose-response curve of this enhanced...
Article
The effects of human leukocyte interferon on BK papovavirus (BKV) infection in 41 recipients of renal transplants were studied as part of a randomized, double-blind, placebo-controlled trial. Eight transplant recipients demonstrated fourfold or greater rises in antibody to BKV, and three excreted BKV in urine. Neither seroconversion nor excretion w...
Article
This chapter reviews the phenomenon of shedding of cell surface macromolecules, its role in normal membrane (glyco)protein turnover, and its importance in certain disease processes. Shedding is especially important in cancer cells where the release of cell surface components, such as proteases and adhesion molecules, occurs continually. The chapter...
Chapter
The explosive growth in the number of laboratories involved in the production of murine monoclonal antibodies in vitro using hybridoma technology (Köhler and Milstein, 1975) is a testimony to the utility of monoclonal antibodies as research tools. It is also clear that monoclonal antibodies produced in vitro are unique reagents which might provide...
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Full-text available
A new mitogenic factor has been isolated from tissue culture grade lactalbumin hydrolysate. Incubation of postconfluent Swiss 3T3 cells in serum-free medium containing lactalbumin hydrolysate resulted in enhanced synthesis and release of plasminogen activator. Sephadex G-100 gel filtration of concentrated, dialyzed lactalbumin hydrolysate revealed...
Article
Stimulation of postconfluent Swiss 3T3 cells in serum-free medium with 4.3 mM Ca2+ results in marked increases in both released and cell-associated plasminogen activator (PA). Increased release of PA commenced approximately 10 to 12 hours post-stimulation and continued to increase steadily until 48 hours at which time the stimulates cells (4.3 mM C...
Article
Herpes simplex virus (HSV) type 1 replicated and persisted in human T, B, and myeloid cell lines with different patterns of viral replication and various effects on cell growth. T cell line CEM supported the replication of HSV for over 400 days without detectable differences in cell growth as compared with uninfected cells. HSV persisted in B cell...
Article
A double-blind, placebo-controlled trial of interferon prophylaxis against viral infections was conducted in renal-transplant recipients receiving standard immunosuprressive therapy with or without antithymocyte globulin. Interferon was administered for six weeks, beginning on the day of transplantation. Cytomegalovirus excretion began earlier and...
Article
The effects of mitomycin C and 60Co gamma-irradiation, which induce production of SV40 from SV40-transformed hamster cells, on the replication of superinfecting SV40 or virus DNA in cells varying in permissivity for SV40 replication have been examined. These agents enhance replication of SV40 in an uninducible line of SV40-transformed hamster kidne...
Article
The effects of mitomycin C and 60Co γ-irradiation, which induce production of SV40 from SV40-transformed hamster cells, on the replication of superinfecting SV40 or virus DNA in cells varying in permissivity for SV40 replication have been examined. These agents enhance replication of SV40 in an uninducible line of SV40-transformed hamster kidney ce...
Article
Peripheral blood leukocytes from three patients with cytomegalovirus (CMV) mononucleosis were examined for their functional capacity in vitro. Cells from the three patients functioned within the expected normal range as measured by phagocytosis, reduction of nitroblue tetrazolium, and chemotaxis. CMV was isolated from the polymorphonuclear-rich cel...
Article
The intracellular distribution of plasminogen activator in growing, confluent, and transformed 3T3 cells was investigated by using sucrose density gradient centrifugation. In confluent cells, which do not release plasminogen activator extracellularly, most of the activity was found in a heavy membrane fraction. In growing and transformed 3T3 cells,...
Article
INTERFERON, as well as inducing an antiviral state, can modify certain other cell characteristics. For example, it has been shown to inhibit cell proliferation1-4 and release of C-type virus5,6, and to enhance the expression of H-2 antigens7,8 and the amount of glycoprotein on the cell surface9. These effects might be explained by decreased release...
Article
The induction by ultraviolet light of simian virus 40 (SV40) from two SV40--transformed hamster kidney cell lines is enhanced by caffeine. In order to investigate the mechanism responsible for this enhancement, the effect of caffeine on postreplication repair of DNA damaged by UV light was studied utilizing alkaline sucrose-gradient sedimentation....
Article
Several clones of simian virus 40 (SV40)-transformed hamster kidney cells, which are heterogeneous for induction of infectious SV40, have been studied. SV40 yields are low after induction with /sup 60/Co ..gamma.. irradiation or mitomycin C. In order to clarify the mechanism(s) by which virus is produced in induced cells, we analyzed the replicatio...
Article
Several aspects of virus-lymphocyte interactions have been reviewed. Some form of lymphocyte activation is required for the replication of viruses that infect the lymphocyte exogenously or are activated from proviral genetic information contained within the host cell genome. Other factors that help determine the outcome of virus–lymphocyte interact...
Article
Peripheral lymphocytes from human volunteers boosted with tetanus toxoid were cultured after in vitro infection with Epstein-Barr virus. Forty-four continuous lymphoblastoid lines were established which continued to secrete human gamma globulin; seven of these secreted antibody to tetanus toxoid. Subcultures derived from limiting dilution experimen...
Article
Cell-mediated and humoral immune responses against antigens associated with primate C-type oncoviruses were evaluated in humans by microcytotoxicity and radioimmunoprecipitation assays. Five of six women tested sequentially during pregnancy developed selective cell-mediated reactivity against baboon endogenous virus (BEV)--infected human fibroblast...
Article
ALTHOUGH little is known about the biochemistry of the formation of sister chromatid exchanges (SCEs), it has been suggested1-5 that they reflect some aspect of cellular DNA repair. Because agents that promote SCE formation (for example, refs 2, 3 and 6-9) also induce infectious virus from certain SV40-transformed hamster cell lines10,11 and becaus...
Article
We have previously reported (1,2) the establishment of a continuous rabbit cell line synthesizing and secreting antibody to type III pneumococcal polysaccharide. This line was established from a simian virus 40 (SV40) transformed spleen cell suspension obtained from a rabbit hyperimmunized with type III pneumococcal vaccine. This approach has not b...
Article
Human peripheral blood leukocytes, lymphocyte subpopulations, and hemic cell lines were examined for their ability to supprot HSV and CMV replication. Mitogen-stimulated mononuclear leukocytes, B lymphocytes, and T lymphcytes supported the replication of HSV to high titers over 3 to 5 days of infection. HSV replicated in unstimulated mononuclear le...
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Full-text available
Actively growing Swiss 3T3 cells secret high levels of plasminogen activator which decreases after the cells become confluent. In contrast, simian virus 40-transformed 3T3 cells secrete large amounts of plasminogen activator independent of cell density (Chou, I.-N., O'Donnel, S.P., Black, P.H., and Roblin, R.O. (1977) J. Cell. Physiol. 91, 31-38)....
Article
The expression of extracellular fibrinolytic activity in untransformed 3T3 cell cultures depends on the growth state of the cells. Actively growing 3T3 cultures exhibit a relatively high level of fibrinolysis, which decreases progressively as the cells become confluent and density-inhibited. The low level of fibrinolytic activity in confluent 3T3 c...
Article
Full-text available
Medium from cultures of simian virus 40-transformed mouse 3T3 cells (SV3T3) inhibits the migration in vitro of peritoneal exudate cells (macrophages) from guinea pigs while medium from untransformed 3T3 cultures does not [Hammond, M. E., Robbin, R. D., Dvorak, A. M., Selvaggio, S. S., Black, P. H. & Dvorak, H. F. (1974) Science 185, 955-957]. The p...
Article
A new adenovirus type 34 was isolated from urine of a renal transplant recipient undergoing immunosuppressive therapy. Isolation of the virus and subsequent seroconversion to this agent coincided with development in the patient of an interstitial pneumonia. The findings suggest that AV34 was either introduced around the time of the transplant, perh...
Article
The interactions between aberrant immune responses and C-type oncornaviruses in mice are complex. These viruses may be activated during certain immune responses, e.g., histocompatibility reactions, in the face of chronic immunosuppression. Oncornaviruses, themselves, may induce autoaggressive cell-mediated responses in certain lymphoid subpopulatio...
Article
Considerable evidence indicates that human cytomegalovirus (CMV), like its murine counterpart, can reside in a latent state within lymphoid cells. Massive transfusions of peripheral blood to normal recipients can lead to seroconversion against CMV antigens, less frequently to atypical lymphocytosis, and uncommonly to heterophile-negative mononucleo...
Article
The effect of caffeine on the uv light induction of SV40 virus from two transformed hamster cell lines heterogeneous for the induction of infectious virus was studied. The amount of virus induced was significantly increased in both cell lines when exposure to uv light was followed by treatment with caffeine. Caffeine in the absence of uv irradiatio...
Article
Simian virus 40-transformed hamster cells were induced to produce infectious virus by treatment with mitomycin C or gamma-irradiation. A portion of the simian virus-40 DNA, which is integrated into the host cell genome in uninduced cells, was recovered in a pool of relatively low-molecular-weight DNA early after induction treatment in the absence o...
Article
Thymocytes from preleukemic mice persistently infected with Moloney murine leukemia virus (MuLV-M-carriers) were vigorously autoaggressive toward normal syngeneic target cells; they exhibited a graded response to allogeneic cells, but they spared xenogeneic cells or syngeneic cells infected with MuLV-M or MuLV-G (Gross). Syngeneic target cells infe...
Chapter
Many experimental tumors, both carcinogen-induced1 and virus-induced,2–5 contain new cellular antigens, generally demonstrable by transplant rejection procedures. Huebner et al.6 first demonstrated the presence of new, noninfectious, complement-fixing (CF) antigens clearly under viral genetic control, in adenovirus-induced tumors in hamsters and ra...
Article
Cloned cell lines have been isolated after simian virus 40 (SV40) transformation of kidney cells of an inbred hamster strain. Considerable heterogeneity for the induction of infectious virus was observed between the lines, ranging from the spontaneous production of infectious virus to nonproducer characteristics. In spite of their differences in vi...
Article
The induction of infectious simian virus 40 (SV40) was studied in synchronized cultures of SV40-transformed hamster cells. Cells were synchronized with a double excess thymidine block and induced by mitomycin C treatment or uv irradiation at hourly intervals after release from the block. Infectious virus was measured in cell-free extracts at 72 hr...
Article
The authors have been studying a murine lymphoma model in which lymphomagenesis apparently results from the unrestrained proliferation of autoaggressive, Moloney leukemia virus (MuLV M) infected, thymus derived (T) cells. Target cells for microcytotoxicity assays consisted of established lines of normal syngeneic, allogeneic and xenogeneic fibrobla...