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Biomedical subjects

H Friedman

Publications and source records attributed to H Friedman.

At least 325 records · Page 18Linked to original sources
PubMed1985

Immune suppression and induction of gamma interferon by pertussis toxin.

It has been suggested that pertussis toxin is a virulence factor of Bordetella pertussis. Although extracts enriched in pertussis toxin activity have been reported to enhance immune responsiveness, other studies have demonstrated a suppressive ability, suggesting that the toxin may contribute to the virulence of B. pertussis through mechanisms involving immune suppression. We report that purified pertussis toxin suppressed the in vitro immunoglobulin M antibody response of mouse splenocytes to sheep erythrocytes. At submitogenic doses, the toxin also suppressed [3H]thymidine incorporation by splenocytes, suggesting that it interfered with antibody formation by inhibiting lymphocyte proliferation. Antiviral activity was detected in culture supernatants obtained from pertussis toxin-suppressed splenocyte cultures by using a cytopathic effect inhibition assay. This antiviral activity was virus nonspecific, sensitive to pH 2.0 treatment, stable to heating at 56 degrees C, and neutralized by anti-gamma interferon antiserum. Finally, the fractionation of splenocytes by anti-immunoglobulin panning techniques suggested that Lyt2+ lymphocytes proliferated in response to pertussis toxin and produced interferon. Our results suggest that pertussis toxin may contribute to the virulence of B. pertussis through stimulation of Lyt2+ lymphocytes, resulting in the induction of gamma interferon and the subsequent inhibition of the primary antibody response.

Animals↗
PubMed1985

Vibrio vulnificus resists phagocytosis in the absence of serum opsonins.

Invasive disease caused by Vibrio vulnificus may result partially from resistance to phagocytic host defense mechanisms. The present studies show that V. vulnificus resists phagocytosis by murine peritoneal macrophages in the absence of serum opsonins and extracellular bacterial products, apparently through the anti-phagocytic properties of the bacterial surface.

Animals↗
PubMed1985

Kinetics and characterization of interferon production by murine spleen cells stimulated with Legionella pneumophila antigens.

Formalin-killed Legionella pneumophila bacterial cells, as well as a purified cell wall preparation (designated F-1 antigen) containing lipopolysaccharide (LPS), stimulated production of interferons (IFNs) in mouse spleen cell cultures. L. pneumophila whole-cell vaccine induced an IFN that was pH 2 labile and neutralized by anti-IFN-gamma indicating that IFN-gamma was the dominant form present. F-1 antigen induced a mixture of IFNs, depending upon the age of the culture and cell types present. In freshly prepared whole-spleen cultures and in 2-h adherent cultures, F-1 induced predominantly IFN-alpha/beta. In whole-spleen cultures that were allowed to age for 24 to 48 h before stimulation, F-1 was seen to induce mostly IFN-gamma, with low levels of IFN-alpha/beta present. Since only IFN-alpha/beta was produced in T-cell-depleted populations (at 2 h or at 48 h), it is suggested that T cells are responsible for IFN-gamma production in aged cultures. Additionally, heat-treated F-1, Escherichia coli LPS, and heat-treated E. coli LPS all induced similar levels of IFN-gamma in whole-splenocyte or nonadherent cell cultures which were incubated 48 h before stimulation. This suggests that LPS present in F-1 is responsible for IFN-gamma production and that an activated cell population is required. These results show that L. pneumophila antigens can induce the production of various types of IFN in mouse spleen cell cultures through several mechanisms.

Animals↗
PubMed1985

Endometriosis detection by US with laparoscopic correlation.

Endometriosis is a common cause of female infertility. It may affect as many as 40% of infertile women and may be the sole contributing factor to infertility in 15%. A study was undertaken to determine the usefulness of the routine pelvic ultrasound (US) examination in the detection of endometriosis by correlating pelvic US findings with laparoscopic findings in 85 patients who underwent both examinations. Forty-eight patients (56.5%) had no laparoscopic evidence of endometriosis, and 37 patients (43.6%) had endometriosis. Eight of the patients had abnormal sonograms; of these patients, only four had sonographic abnormalities that corresponded to laparoscopically identified endometriosis. Thus, US was successful in detecting endometriosis in only four (10.8%) of 37 patients. US is neither sensitive nor specific in diagnosing endometriosis. Furthermore, we believe that US does not have a significant role in the diagnosis or management of endometriosis in patients in whom a pelvic mass or other obvious pelvic abnormality is not suspected.

Adnexal Diseases↗
PubMed1985

The role of imaging in infertility management.

In a retrospective review of 211 female infertility patients receiving ovulation induction agents, the role of sonography in infertility management is defined. Sonography is used to determine imminence of ovulation for timing of insemination and in vitro fertilization. It is also used to diagnose ovarian hyperstimulation syndrome. To identify characteristics of the ovarian follicles of women able to conceive that might differentiate them from those unable to become pregnant, patients were assigned to "pregnant" (30.8%) or "nonpregnant" subgroups. In 259 sonographically monitored cycles reviewed, follicular size and configuration were not different for the two groups. The cumulus oophorus was seen in 28% of pregnant patients (8/28) and in only two nonpregnant patients. Low-level echoes were seen in the mature follicles of 11 patients but not in the large follicles of nonpregnant patients. Low-level intrafollicular echogenicity may be a prognostic indicator of fertility and may represent a periovulatory state, optimal, in the appropriate clinical setting, for artificial insemination or in vitro fertilization.

Adult↗
PubMed1985

The effect of delta-9-tetrahydrocannabinol and 11-hydroxy-delta-9-tetrahydrocannabinol on T-lymphocyte and B-lymphocyte mitogen responses.

Previous studies have shown that delta-9-tetrahydrocannabinol (THC) suppresses T-lymphocyte proliferation when added to human cell cultures. We report that THC when added to mouse splenocyte cultures suppressed T-lymphocyte (Con A, PHA) and B-lymphocyte (LPS) mitogen-induced proliferation. Although the ED50 concentrations (5 micrograms/ml; 1.6 X 10(-5)M) of THC were similar for suppressing all three mitogen responses, higher threshold concentrations of drug were required to effect suppression of the T-lymphocyte mitogen responses. Complete suppression of T- and B-lymphocyte responses was achieved with THC concentrations (8 micrograms/ml or 2.6 X 10(-5)M) which were not directly toxic as judged by vital dye exclusion. The hydroxylated metabolite of THC, 11-hydroxy-THC, was observed to be much less potent in the inhibition of lymphocyte proliferation. However, as with the parent compound, B-lymphocyte responses appeared to be the most affected by the drug. Additional studies demonstrated that both T- and B-lymphocyte proliferation is rapidly suppressed following THC treatment, not affected by a 24 hr. pretreatment with THC, and not as readily suppressed by THC in cultures containing 20% serum. Thus, THC appears to inhibit both T- and B-lymphocyte proliferation with B-lymphocyte responses displaying greater inhibition at lower drug concentration. The 11-hydroxy metabolite is much less suppressive in this system than the parent compound.

Animals↗
PubMed1985

Impaired in vitro interferon, blastogenic, and natural killer cell responses to viral stimulation in acquired immune deficiency syndrome.

The in vitro immune response to herpes simplex virus (HSV), type 1, strain 539, HSV type 2, strain 316D, and cytomegalovirus was studied in 20 patients (14 with acquired immune deficiency syndrome, four with the acquired immune deficiency syndrome-related symptom complex, and two sexually active asymptomatic homosexuals) and 18 heterosexual healthy controls. Peripheral blood mononuclear cells were cultured with 2 X 10(5) plaque-forming units of heat-inactivated viruses, their lymphocyte blastogenic responses were measured after 5 days in culture by [3H]-thymidine incorporation, their interferon production was measured after 24 hr and 5 days, and natural killer (NK) cell activation was measured after 24 hr and 5 days of culture. Blastogenic responses to viruses were significantly low for only HSV, type 1:1.75 X 10(3) cpm in patients' cells compared to 6.36 for controls. Interferon responses to all three viruses were significantly low at both 24 hr and 5 days; e.g., HSV, type 1:139 IU/ml in patients' cells compared to 777 for controls at 24 hr. NK cell responses of patients were lower than those of controls when tested fresh and after 24 hr of incubation: 6.1 versus 11.7% and 9.2 versus 16.8% target cell lysis, respectively. Exposure to viruses boosted NK cell responses of both patients' and controls' cells, but boosting was generally greater among the normal rather than the patients' cells. The abnormalities of response were present in all three patient groups. Addition of interleukin-2 in vitro increased the patient and control blastogenic and NK responses but did not augment the interferon responses. The in vitro responses to both HSV, type 1, and HSV, type 2, correlated significantly with our conventional assays of the percentage and absolute level of T4+-helper lymphocytes in the blood and the blastogenic responses to mitogens, such as phytohemagglutinin, pokeweed mitogen, and concanavalin A. This system should be useful for the study of host defense in acquired immune deficiency syndrome patients and those in high-risk groups, and also for the in vitro evaluation of immunomodulators.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Macrophage-mediated natural cytotoxicity of dimethyl sulfoxide-treated Friend erythroleukemia cells.

Dimethyl sulfoxide (DMSO) treatment of the Friend erythroleukemia cell line GM 979 markedly increased its susceptibility to natural cytotoxicity by splenocytes from normal inbred DBA/2 mice. Cytotoxicity occurred with normal adherent spleen cells as well as dextran-elicited peritoneal exudate (PE) cells but not with resident PE cells. Susceptibility of the leukemia cells to natural cytotoxicity increased to maximum levels upon treatment with 210 mM DMSO for 2-3 days. The natural cytotoxicity assayed by the 51Cr release procedure was first detectable after 9 hours of incubation and reached maximum levels by 24-30 hours. Although both DMSO and n-butyric acid induced rapid erythroid cell differentiation of the GM 979 cells, and both resulted in increased hemoglobin synthesis, only DMSO treatment enhanced the susceptibility of the cells to natural cytotoxicity by normal splenocytes. Cell-free supernatants from adherent spleen cells cocultured with DMSO-treated GM 979 cells for 6-15 hours were markedly cytotoxic for cultures of other chromium-labeled DMSO-treated leukemia cells. Supernatants from cultured adherent spleen cells alone, or lysates of DMSO-treated leukemia cells, did not possess cytotoxic activity. Resident peritoneal macrophages also had no cytotoxic activity against DMSO-treated cells, and culture supernatants from resident PE cells, even after incubation with DMSO-treated target cells, failed to show significant levels of cytotoxicity. These results indicate that normal splenic adherent cells as well as elicited PE cells have the ability to lyse DMSO-treated leukemia cells.

Animals↗
PubMed1985

Biological effects of White-type polysaccharides of gram-negative bacteria.

The White-type polysaccharide (WPS), often called Freeman polysaccharide, was obtained by hydrolyzing gram-negative bacteria in 0.2 N acetic acid at 100 degrees C for 2 h. The crude product contained partially degraded O-antigens as well as other components that were active as immune adjuvants, enhancers of macrophage cytotoxicity of tumor target cells, and inducers of osteoclastic bone resorption. The same WPS preparation augmented the tumor cytotoxicity of normal mouse spleen cells and slightly retarded the take of L1210 leukemia in mice. The WPS preparations generated colony-stimulating factor in mice but were not active in lymphoproliferative (mitogenicity) tests. Chemical analyses of the WPS preparations did not detect the presence of components characteristic of the lipid moiety of endotoxins. The WPS samples were also negative in biological assays of endotoxicity such as local Shwartzman and toxicity tests. These findings indicate that gram-negative bacteria contain nonendotoxin components that are potent modifiers of some biological responses.

Actinobacillus↗
PubMed1984

Production of an insulin-like growth factor by osteosarcoma.

To test the possibility that osteosarcoma cells produce their own growth factors, we measured levels of insulin and somatomedin C (SMC), an insulin-like growth factor, in culture media of two cell lines derived from patients with that disease. SMC but not insulin levels increased three- to ten-fold over a period of 7 days paralleling the increases in cell number. Production of SMC was inhibited by cycloheximide.

Cell Division↗
PubMed1984

Cell-mediated immune responsiveness to cardiac extracts by peripheral blood leukocytes from patients after myocardial infarction or open-heart surgery.

A microdroplet in vitro procedure measuring migration inhibition was utilized to assess cell-mediated immune reactions by peripheral blood leukocytes from patients after myocardial infarction or cardiac surgery. The antigen preparations were derived from human cardiac tissue. Whereas whole-cell extracts and human myoglobin preparations had little effect on migration, mitochondrial preparations markedly inhibited the migration of blood leukocytes from a majority of the patients. Inhibition of migration appeared to reflect development of cell-mediated immunity to heart antigens after myocardial infarction or surgery. These results extend observations of anticardiac immune development in patients following cardiac injury. Two patients demonstrated a direct relationship between enhanced migration inhibition and clinical disease. It is likely that autoreactive responses to cardiac tissue may be involved and influence subsequent physiological events following initial cardiac infarction or surgery.

Adolescent↗
PubMed1984

Legionella pneumophila-induced blastogenesis of murine lymphoid cells in vitro.

Legionella pneumophilia antigen preparations, either killed whole cell vaccine, a soluble sonic extract, or a purified large-molecular-weight somatic antigen, stimulated blastogenic responses by splenocytes from both normal and Legionella-sensitized mice. Graded amounts of the bacterial preparations, when added to cultures of normal spleen cells, resulted in increased uptake of thymidine into cellular DNA, indicating that the preparations were mitogenic for normal mouse splenocytes. Spleen cells from mice injected with graded numbers of living bacteria showed blastogenic responsiveness to Legionella preparations generally at a higher level than spleen cells from normal animals. The heightened blastogenic response was mainly evident with spleen cells obtained from mice injected with living bacteria 2 to 3 weeks earlier. Splenocytes from mice infected with legionella less than 1 to 2 weeks or for more than 4 to 5 weeks responded generally similar to those obtained from uninjected mice, indicating that sensitization with living organisms had a relatively short duration. Spleen cell suspensions responding to the L. pneumophila antigens appeared to be mainly B-lymphocytes since cell suspensions from athymic nude mice deficient in T-cells responded as well as cells from conventional mice. Furthermore, passage of splenocytes over nylon wool columns to obtain B-cell-enriched preparations resulted in cell populations capable of responding to Legionella antigen. The cell fractions rich in T-cells were much less capable of responding to the Legionella antigens. In addition, treatment of spleen cell populations with antitheta serum plus complement failed to inhibit the blastogenic response, whereas the same spleen cell preparations treated with anti-mouse immunoglobulin serum plus complement markedly diminished blastogenic responsiveness, again consistent with the likelihood that B-lymphocytes were the major cell class responding to the Legionella preparations.

Animals↗