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Biomedical subjects

V Barak

Publications and source records attributed to V Barak.

At least 109 records · Page 6Linked to original sources

Interleukin-1: local production and modulation of human granulosa luteal cells steroidogenesis.

OBJECTIVES: To investigate the possibility of local interleukin-1 (IL-1) and IL-1 inhibitor production by human granulosa and cumulus cells and to assess their direct effects on the steroidogenesis of these cells in vitro. DESIGN: Prospective study. PARTICIPANTS: Normal ovulatory women undergoing ovulation induction for in vitro fertilization. INTERVENTION: Pretreatment of patients with gonadotropin-releasing hormone analogue, human menopausal gonadotropin, and human chorionic gonadotropin (hCG). MAIN OUTCOME MEASURES: Retrieval and isolation of granulosa luteal cells and follicular fluid (FF). Granulosa luteal cells and cumulus cells cultured and analyzed by fluorescent activated cell sorter. Follicular fluid separated and bioassayed for IL-1 and IL-1 inhibitory activity. Steroid measurement performed. Interleukin-1 inhibitor purified. Interleukin-1 and IL-1 inhibitor bioassay performed. Statistical analysis made and interpreted. RESULTS: Interleukin-1, but not IL-1 specific inhibitory activity, was found in granulosa and cumulus cell cultures and also in FF, only after its purification on a high-pressure liquid chromatography column. Under nonstimulated conditions, neither IL-1 nor IL-1 inhibitor had any effect on basal progesterone (P) or estradiol (E2) secretion. However, IL-1 inhibitor demonstrated significant (P < 0.01) inhibition of hCG-stimulated P secretion (from 200 to 110 ng/10,000 cells per 24 hours). In addition, IL-1 demonstrated a significant (P < 0.05) and dose-dependent inhibition of hCG-stimulated E2 production (from 6,832 +/- 460 to 4,237 +/- 141 pg/10,000 cells per 24 hours). CONCLUSIONS: Interleukin-1 may exert a significant local autocrine regulatory role in the human ovary.

Cells, Cultured↗

The correlation of interleukin 1 and tumour necrosis factor to oestradiol, progesterone and testosterone levels in periovulatory follicular fluid of in-vitro fertilization patients.

Data has accumulated suggesting reciprocity between cytokines and the reproductive system. The present study was performed in order to evaluate the correlation between interleukin 1 (IL-1) and tumour necrosis factor (TNF) concentrations in follicular fluid and its oestradiol, progesterone and testosterone levels. A total of 39 follicular fluid samples, from eight patients undergoing in-vitro fertilization and embryo transfer were evaluated. All of the patients were treated by a midluteal (long) protocol involving a gonadotrophin releasing hormone agonist (GnRHa) coupled with follicular phase human menopausal gonadotrophin. Mean levels in follicular fluid of IL-1, TNF, oestradiol, progesterone and testosterone were 1.58 +/- 0.42 fmol/0.1 ml, 4.69 +/- 4.18 pg/ml, 28.5 +/- 58.1 ng/ml, 2360.5 +/- 2846.3 ng/ml and 7.22 +/- 7.08 ng/ml respectively. There was a significant (P less than 0.01) positive correlation between IL-1 and progesterone levels. There was no significant correlation between the different lymphokines and oestradiol secretion, oocyte fertilization, embryo quality and pregnancy rates. It is concluded that IL-1 and TNF exist in follicular fluid. It may be hypothesized that IL-1 has a local regulatory action, possibly promoting luteinization.

Adult↗

The correlation between interleukin 2 and soluble interleukin 2 receptors to oestradiol, progesterone and testosterone levels in periovulatory follicles of in-vitro fertilization patients.

The present study was performed to evaluate the correlation between follicular fluid levels of interleukin 2 (IL-2) and IL-2 soluble receptor (sIL-2R), oestradiol, progesterone and testosterone levels, oocyte fertilization, embryo quality and pregnancy rates. Twenty-eight patients with a pure tubal factor and undergoing in-vitro fertilization and embryo transfer were randomly chosen and treated with gonadotrophin releasing hormone agonist (GnRHa) in the midluteal phase (long protocol) coupled with follicular phase administration of human menopausal gonadotrophin. Transvaginal follicular aspiration was performed 36 h after human chorionic gonadotrophin administration, followed 48 h later by embryo transfer. One hundred and twenty-three follicular fluids were sampled. The mean follicular fluid levels (+/- SD) were 2.30 +/- 0.80 fmol for IL-2, 458.2 +/- 236.0 units/ml for sIL-2R, 28.5 +/- 58.1 ng/ml for oestradiol, 2360.5 +/- 2846 ng/ml for progesterone and 7.22 +/- 7.08 ng/ml for testosterone. There was a significant (P less than 0.01) correlation between IL-2 and testosterone levels. No correlation was found between the lymphokines and serum oestradiol, follicular fluid progesterone, oocyte fertilization, embryo quality and pregnancy. It may be concluded that significant concentrations of IL-2 and sIL-2R exist in follicular fluid. Wide variations in follicular IL-2 and sIL-2R concentrations of different follicles were found in the same patients.

Estradiol↗

Elevated serum levels of soluble tumour necrosis factor receptors (sTNF-R) in patients with HIV infection.

Serum levels of the soluble form of tumour necrosis factor receptor type II (p75) (sTNF-R) were determined in HIV-infected individuals and risk groups and were then correlated with the course of infection and prognosis. sTNF-R levels were determined by an ELISA with MoAbs and polyclonal antibodies to urine-derived sTNF-R proteins. The mean +/- s.e. levels of sTNF-R in the sera of 49 HIV+ male homosexuals, 34 HIV- male homosexuals and 44 matched controls were 6.1 +/- 0.3 ng/ml, 4.4 +/- 0.3 ng/ml and 3.4 +/- 0.2 ng/ml, respectively. All these values were significantly different between each of the groups (P less than 0.001-0.05). Sequential studies of sTNF-R revealed higher levels following seroconversion in 5/8 individuals, remained persistently high during the asymptomatic phase of the infection and became even more elevated in some ARC and AIDS patients. At the same time TNF-alpha was undetectable in sera obtained from HIV+ male homosexuals and from healthy controls. This was independent of stage of HIV infection, serum sTNF-R level and type of ELISA kit used. These findings suggest that TNF-alpha/TNF-R system is turned on before and during HIV infection and raise the possibility that sTNF-R, the natural inhibitor of TNF, may be of importance in determining the course and probably prognosis of the disease.

Enzyme-Linked Immunosorbent Assay↗

Serum soluble interleukin-2 receptor levels are associated with clinical disease status and histopathological grade in non-Hodgkin's lymphoma and chronic lymphocytic leukemia.

Serum soluble Interleukin-2 receptor levels (sIL-2R) were measured in 121 patients (pts) with non-Hodgkin's lymphoma (NHL) and in 30 patients with Chronic lymphocytic leukemia (CLL). Sera collected from 32 normal volunteers and 18 patients with infection or a variety of non malignant hematological disorders served as controls. A small number of patients with Hairy cell leukemia (HCL) and Hodgkin's disease (HD) were also studied. NHL patients were classified according to their clinical status as "active" (82 pts) or "non-active" (39 pts) and CLL according to the stage of their disease. NHL patients were also further classified as low (55 pts), intermediate (38 pts) and high grade malignancy (28 pts), according to the Working formulation scheme. A significant difference was found between the high levels of sIL-2R in patients with "active" disease and the lower levels in patients with quiescent or responsive disease. Significantly different high levels were found in patients with aggressive (intermediate and high grade) lymphoma as opposed to low grade lymphoma and CLL. In CLL itself higher levels of sIL-2R were seen in more advanced disease than in early disease. Thirteen patients with active Hodgkin's disease (HD) had moderately elevated sIL-2R levels, similar to those recorded for patients with infections and some non-malignant hematological disorders while another 13 HD patients in remission, had normal levels comparable to those recorded in normal controls. Extremely high levels of sIL-2R were seen in 2 patients with HD with severe viral infections and levels approaching those seen in HCL, were noted (20-30,000 u/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Recombinant human interleukin-1 suppresses lipoprotein lipase activity, but not expression of lipoprotein lipase mRNA in mesenchymal rat heart cell cultures.

The effect of human recombinant interleukin-1 (IL-1) on the regulation of lipoprotein lipase (LPL) was studied in rat heart mesenchymal cell cultures. A time-dependent reduction in enzyme activity occurred with a 30% fall after 1 h. The suppression of enzyme activity was accompanied by a commensurate reduction in enzyme mass. The reduction in LPL activity was most prominent in the heparin releasable pool; IL-1 treatment resulted in a 7.2-8.3-fold decrease in the functional compartment and a 2.5-2.8-fold decrease in residual cellular activity. The effect of IL-1 could be prevented by the addition of the IL-1 inhibitor. However, in contradistinction to the effect of tumor necrosis factor (TNF), there was no change in LPL mRNA in cultures treated with IL-1. The present results show that the regulation of LPL in mesenchymal heart cell cultures by IL-1 occurs posttranscriptionally, as has been shown in 3T3 cells. The more pronounced effect on LPL activity in the functional pool suggests that IL-1 treatment might have influenced also the processing and/or transport of the enzyme to the cell surface.

Animals↗

Fat necrosis below musculocutaneous flap mimicking carcinoma of breast.

The increasing rate of breast reconstruction after modified radical mastectomy has led to the adoption of several techniques including transverse rectus abdominis musculocutaneous flap. Although the method creates a life-like breast both in texture and appearance, among other complications resulting from this operation, fat necrosis mimicking carcinoma on mammography clearly is common. We focus on the case history of 1 patient and detail our findings.

Breast Neoplasms↗

Susceptibility of Legionella pneumophila grown extracellularly and in human monocytes to indole-3-propionic acid.

Indole-3-propionic acid (IPA), a phytohormone derivative, is a potent inhibitor of growth of Legionella pneumophila cultivated extracellularly in a chemically defined hypotonic medium and intracellularly in human monocytes. The inhibitory activity turns into bactericidal activity with increasing concentrations. The susceptibility of the microorganism to IPA was more evident in "fast-growing" cultures (under conditions of vigorous shaking) than in static cultures growing under an atmosphere of 5% CO2-95% air, which resulted in a decreased growth rate. The MIC, after incubation with the drug for 48 h and as determined by counting of the CFU, was 1.58 microM for fast-growing cultures and 2.64 microM for those grown under static conditions. The MBCs were 5.28 and 26.43 microM, respectively. Tryptophan (Trp) at 150 microM prevented the inhibition caused by 2.64 microM IPA, increased the MIC about 3-fold, and increased the MBC by 10-fold. The effect of Trp was less remarkable in "slow-growing" cultures. The susceptibility of L. pneumophila proliferating in human monocytes was markedly lower than that when it was cultivated extracellularly in the chemically defined hypotonic medium. The MIC after incubation for 48 h was 5.28 microM, and a decrease in viable count was achieved with 105.70 microM. The lower susceptibility was apparently due (at least partially) to the presence of Trp (24.50 microM) in the RPMI 1640 medium that was used for the monocyte cultures. The effect of IPA was time dependent, and prolonged exposure enhanced the bactericidal activity and turned the inhibitory dose into a bactericidal dose. The present data demonstrate that IPA is a potent anti-L. pneumophila factor, although it has a markedly lower activity against bacteria growing intracellularly compared with its activity against extracellularly proliferating microorganisms.

Cells, Cultured↗

The specific IL-1 inhibitor from the human M20 cell line is distinct from the IL-1 receptor antagonist.

Several inhibitors of IL-1 have been described. Four appear to be the same: one purified from urine of patients with monocytic leukemia, another from IgG-stimulated monocytes, a third from PMA-induced U937 cels, and a fourth from keratinocytes. Because these IL-1 inhibitors compete with bona fide IL-1 for occupancy of IL-1 receptors, they are now called the IL-1 receptor antagonist (IL-1ra) or IL-1 receptor antagonist protein (IRAP). We have described another IL-1-specific inhibitor produced by the human myelomonocytic leukemia cell line, M20. This inhibitor specifically blocks IL-1-induced effects both in vitro and in vivo. In the present study, we compared the M20 IL-1 inhibitor with IL-1ra using neutralization in an IL-1 bioassay and immunoblotting with an anti-IL-1ra antibody that recognizes natural IL-1ra. Neutralization experiments, immunoblotting, and western blotting obtained after transfer from SDS-PAGE revealed that anti-IL-1ra does not recognize the M20 IL-1 inhibitor. In addition, the isoelectric point and molecular weight of the M20 IL-1 inhibitor were different from those of the IL-1ra. From these data, we conclude that the M20 IL-1 inhibitor is antigenically unrelated to the IL-1ra but is a distinct and specific IL-1 inhibitor.

Biological Assay↗

Bone marrow stromal elements in murine leukemia: decreased CSF-producing fibroblasts and normal IL-1 expression by macrophages.

A study of bone marrow stromal elements in murine acute myeloid leukemia (AML) was carried out. Our previous studies had indicated marrow stromal deficiency in murine AML. In the current investigation, separate stromal cells were cultured and the results obtained have shown that, while marrow stromal macrophages are normal in leukemia and express adequate amounts of IL-1, the fibroblasts are markedly reduced. However, if sufficient fibroblasts are pooled in vitro, they produce adequate amounts of CSF. Test of TNF alpha in leukemic cells CM, as possible cause of marrow stromal inhibition in leukemia, had not disclosed this cytokine. Further, it was observed that total body lethal irradiation of leukemic mice aggravates the stromal deficiency, confirming results of our previous investigations. It is concluded that bone marrow stromal deficiency in murine AML is due to decreased fibroblasts and, implicitly, reduced CSF production.

Animals↗

Effect of interleukin-1 on adrenocortical activity in intact and hypothalamic deafferentated male rats.

The present study was designed to elucidate the site of action of interleukin 1 (IL-1) modulation of the hypothalamic-hypophyseal-adrenal (HHA) axis. An intraperitoneal injection of recombinant human IL-1 beta (160 U/rat) significantly elevated serum levels of ACTH and corticosterone (CS). In rats with complete mediobasal hypothalamic deafferentation, the HHA response to IL-1 was inhibited. An intracerebroventricular injection of rIL-1 (2 U/rat) caused a marked increase in serum ACTH and CS. These results suggest that IL-1 activates the HHA axis by a direct effect upon the brain, and that intact neural connections between the mediobasal hypothalamus and extrahypothalamic brain regions are essential for IL-1-induced HHA responses.

Adrenocorticotropic Hormone↗

Solitary nonparasitic cyst of the liver: a rare cause of abdominal distension.

Solitary nonparasitic liver cysts are clinically rare, and fewer than 900 patients have been documented over the years. A case is described of a female patient with a large solitary cyst containing 7 L of fluid, which was treated successfully by unroofing. The literature relating to the clinical features, incidence, pathogenesis, histopathology, diagnostic imaging, and surgical management of such cysts is reviewed.

Abdomen↗

Interleukin 1 inhibitory activity secreted by a human myelomonocytic cell line (M20).

Culture supernatants from a myelomonocytic cell line (M20) were found to inhibit interleukin 1 (IL 1) activity in vitro. The factor, isolated from these supernatants, inhibited augmentation of phytohemagglutinin response of mouse thymus cells induced by IL 1 derived from several established cell lines. Various IL 1-dependent activities such as lymphocyte and fibroblast proliferation in vitro were also inhibited by the factor. The factor did not inhibit IL 2-induced or other proliferative responses not related to IL 1. Preliminary biochemical characterization of the factor indicated that the activity resides in a protein with a molecular mass of 52 kDa.

Cell Division↗