Glutamatergic Receptors Modulate Normoxic but Not Hypoxic Ventilation and Metabolism in Naked Mole Rats.

Naked mole rats () are among the most hypoxia-tolerant mammals, but their physiological responses to acute and chronic sustained hypoxia (CSH), and the molecular underpinnings of these responses, are poorly understood. In the present study we evaluated the acute hypoxic ventilatory response and the occurrence of ventilatory acclimatization to hypoxia following CSH exposure (8-10 days in 8% O) of naked mole rats. We also investigated the role of excitatory glutamatergic signaling in the control of ventilation and metabolism in these conditions.

Incidence of autoantibodies against type I and type II interferons in a cohort of systemic lupus erythematosus patients in Slovakia.

Autoantibodies against interferon (IFN) can be found in patients with systemic lupus erythematosus (SLE). However, detailed information about the occurrence of type-specific antihuman IFN antibodies is not available. In this study, we investigated the incidence of autoantibodies specifically recognizing various type I IFNs (alpha1, alpha2, beta, omega) and type II IFN (gamma).

Increased effects of topically applied interferon on herpes simplex virus-induced lesions by caffeine.

Caffeine (Cf, 0.15-0.6 mg/ml) and human leukocyte interferon (IFN, > 5 x 10(2) IU/ml) partially inhibited the replication of herpes simplex virus type 1 (HSV-1) in human diploid LEP cells and HaCaT cells.

Porcine leukocyte interferon exhibits close antigenic relatedness to human interferon alpha 2, but not to human interferon alpha 1.

As reported by others using polyclonal antisera, natural human and porcine interferons (IFN)-alpha are antigenically related. Using monoclonal antibodies (mAb) in neutralization and ELISA experiments, we found differences in the subtype/antigenic composition between virus-induced porcine and human leukocyte preparations. Human leukocyte IFN-alpha contains two major antigenically distinct subtypes, IFN-alpha 1 and IFN-alpha 2.

Cytokines: the fourth homeostatic system.

The cytokines represent a network of small polypeptides produced by a variety of immune, blood and somatic cells. They can be considered the fourth homeostatic system serving the integrity of the organism. The cytokines cooperate with, substitute or, regulate the activity of cells and products of hormonal, neural and immune systems and function as physiological and/or emergency regulators.

Peptide-mapping of three neutralizing epitopes into predicted biologically active sites of human interferon-alpha 2.

Immunologically less reactive but functionally relevant structures were identified on human interferon (IFN)-alpha 2 by three neutralizing monoclonal antibodies (mAb). The binding sites of these mAbs were mapped using a set of synthetic peptides that covered the amino acid sequence of two predicted biologically active segments in the regions 31-53 and 63-85 of IFN-alpha 2. We measured the capacity of fragments to inhibit the IFN-neutralizing activity of mAbs and located three linear epitopes around residues 42-53, 63-76 and 77-85 of the IFN-alpha 2 molecule.

In vitro antiproliferative effect of interferon alpha in solid tumors: a potential predictive test.

An in vitro test for the antiproliferative effect of human leukocyte interferon (IFN-alpha) was performed in primary cultures of tumor cells obtained from 32 patients with either malignant melanoma (13), renal carcinoma (4) or bladder carcinoma (15). Our results demonstrated activity of IFN in all three groups of solid tumors. However, appreciable differences in sensitivity to antiproliferative effect of IFN between individual tumors of the same type were found.

Cytokines in health and disease.

Cytokines are cellular regulators of non-immunoglobulin character. The studies of interferon, a representative cytokine, support the view that cytokines are information molecules forming a network in the animal organism. Their main task is to protect the homeostasis of the organism.

Immunodominant structures in the aminoterminal portion of human interferon alpha 1.

The analysis of the antigenic structure of human interferon (IFN)-alpha 1 with a panel of monoclonal antibodies revealed four immunodominant regions. Three of them, recognized by 12 of 14 antibodies were mapped into the aminoterminal portion of IFN-alpha 1 around residues 31-38, 43-53 and 63-85. The region 31-85 proved important also for the antiviral and antiproliferative activity of the IFN-alpha 1 molecule.

Distinct effect of pH 2 on a common antigenic structure found in human interferons-alpha 1 and -alpha 2 in the region 30-35.

The antigenic similarity between molecules of recombinant human interferon-alpha 1 (IFN-alpha 1) and recombinant human IFN-alpha 2 was demonstrated with neutralizing monoclonal antibody (mAb) 1-46. The common epitope for the mAb 1-46 was localized into amino-terminal region of IFN-alpha molecule around residues 30-35. Following pH 2 treatment, the biological activity of both IFN-alpha 1 and IFN-alpha 2 was retained but the antigenic relatedness between corresponding sequences 30-35 was diminished.

Mapping of two immunodominant structures on human interferon alpha 2c and their role in binding to cells.

Structure-function studies of human recombinant interferon (IFN) alpha 2c were performed using a panel of specific monoclonal antibodies in the binding and neutralizing assays. Two immunodominant structures, designated sites I and II, were detected and localized within two conserved hydrophilic regions of IFN-alpha molecule. Using the NK2 antibody as a marker, site I was mapped into a carboxy-terminal domain around residues 112-148.

Enhancement of neutralizing efficacy by combining three monoclonal antibodies to human interferon-alpha.

Three murine monoclonal antibodies (mAb) directed to distinct epitopes on recombinant human interferon (IFN)-alpha 1, and three mAb recognizing distinct epitopes on recombinant human interferon (IFN) alpha 1, and three mAb recognizing distinct epitopes on recombinant human IFN-alpha sc, were studied by IFN-neutralizing assays. The efficacy of neutralization of the anti-viral and the anti-proliferative activities of IFN-alpha 1, or IFN-alpha 2c, by the specific antibodies used, individually or in combination, were evaluated. In comparison with single mAb, the mixtures of three mAb against IFN-alpha 1 or three mAb against IFN-alpha 2c were capable of neutralizing more than 10-times larger amounts of IFN-alpha 1 and alpha 2c, respectively.

Are the acid-labile interferon alpha and interferon omega-1 identical?

The interferon (IFN) activity found in human leukocyte IFN alpha preparations, autoimmune and AIDS sera, and others was reported to have distinct antigenic and deviating biological properties. This led to its vague designation as acid-labile and thermolabile IFN alpha. However, using specific monoclonal antibodies, the acid-labile component of IFN alpha (not exposed to pH 2) and recombinant IFN omega 1 showed significant relatedness.

Modification of the antigenic structure of human interferon alpha-2 by PH 2 treatment: a further support for the antigenic relationship between alpha and beta interferons.

We have recently reported that a unique antigenic structure, designated as Common epitope 1, was found to be shared by human recombinant IFN alpha-2 and the human fibroblast IFN beta. The Common epitope 1 was identified with the aid of a synthetic IFN alpha-2 fragment SH 132-137. Based on this observation, we proposed the hypothesis that an antigenic relationship should exist also between natural human leukocyte IFN alpha and natural human fibroblast IFN beta.

Antigenic link between human interferons-alpha and -beta: the common epitope 1.

An until now unobserved consistent antigenic structure, tentatively named "common epitope 1," was detected on molecules of human recombinant (rHu) IFN-alpha 2 and natural HuIFN-beta by testing with monoclonal and polyclonal antibodies. The monoclonal antibody B6, obtained after immunization of BALB/c mice with human fibroblast IFN-beta, was capable of binding and neutralizing both IFN-alpha 2 and natural IFN-beta. The neutralizing activity of monoclonal antibody B6 was completely inhibited by a synthetic hexapeptide which corresponded to the amino acid sequence of IFN-alpha 2 in positions 132-137.

Murine monoclonal antibodies against human fibroblast (beta) interferon. Correlation of the neutralization of antiviral and antiproliferative activities.

Eight mouse hybridoma lines secreting monoclonal antibodies (MoAb) to human fibroblast interferon (HuIFN-beta) were established. All MoAbs were capable of neutralizing two different biological activities of HuIFN-beta: the antiviral activity and the antiproliferative activity. Positive correlation was demonstrated between the ability of hybridoma culture supernatants to neutralize the antiviral and antiproliferative effects of human fibroblast IFN.

Human acid- and thermolabile alpha-interferon-like substance: selective reactivity with a monoclonal antibody.

An acid- and thermolabile alpha-interferon-like substance, designated AL-IFN-alpha, has been found in non-processed normal human leukocyte IFN preparations as well as sera from patients with autoimmune or other chronic diseases. Little is known about origin, production and biological activity of these IFN activities. Monoclonal antibodies were obtained which proved highly selective in neutralizing AL-IFN-alpha in both anti-proliferative and antiviral tests.

Abnormal macrophages and NK cell cytotoxicity in human systemic lupus erythematosus and the role of interferon and serum factors.

Macrophage (MO) and natural killer (NK) cell mediated cytotoxicity to K562 target cells were strikingly decreased in patients with systemic lupus erythematosus (SLE). SLE NK cells failed to release soluble factor(s) for lysing the targets. IFN-induced enhancement of both types of cytotoxicity was impaired.

Interferon after 30 years.

IFN is a product of a growing family of IFN-genes in the vertebrate cell. It is a polypeptide which fits the definition both of lymphokines and/or "local" hormones, and, cannot be anymore considered an "autonomous antiviral factor", as postulated originally. Rather, IFN increasingly seems to play in the organism the role of a "master-lymphokine" that mediates, potentiates or regulates the effects of various lymphokines in differentiation, growth and antigen expression of cells.

Monoclonal antibodies neutralizing human leukocyte acid- and thermolabile interferon alpha.

Using a high titred human leukocyte IFN alpha preparation which contained both acid- and thermolabile (AL-IFN alpha) and acid- and thermostable IFN alpha species in 9:1 proportion for immunization of BALB/c mice, five hybridomas secreting monoclonal antibodies that reacted with AL-IFN alpha were obtained. In antiviral and antiproliferative tests on HL-60 cells, their products showed high degree of specificity for AL-IFN alpha. The results suggest that both the "normal" leukocyte AL-IFN alpha and the IFN alpha found in sera of autoimmune and other chronic patients might belong to the same subtype of IFN alpha.

Monoclonal antibodies neutralizing the antiviral and the antiproliferative activities of human interferon gamma.

Spleen cells from BALB/c mice immunized with human leukocyte interferon gamma (HuIFN-gamma) were fused with mouse NSO myeloma cells. Nine hybridoma lines were found secreting monoclonal antibodies (MoAb) which were able to neutralize the antiviral activity of HuIFN-gamma. All nine MoAb inhibited also the antiproliferative activity of HuIFN-gamma.

Activation of NK cells in subjects exposed to mild hyper- or hypothermic load.

The effect of mild hyper- and hypothermic stress on release of selected hormones (somatotropin, noradrenaline, etc.), interferon (IFN), and activity of NK cells in the blood was examined in groups of young males during a 30 min exposure to 39 degrees C and 4 degrees C. A quick release of somatotropin was registered in 44% of examinees in the hyperthermic group, while the persons exposed to 4 degrees C reacted with a release of noradrenaline only.

Human interferon alfa therapy and hepatitis B virus markers in the serum of patients with chronic course of illness.

Dynamics of serum levels of HBsAg, HBeAg and anti HBc were followed during human interferon alpha (Hu IFN alpha) therapy of patients with chronic active or chronic persistent hepatitis B. More or less expressed oscillations of HBsAg serum levels seen in two out of our six treated patients seemed to occur due to IFN effect. Little and seldom changes were observed in HBeAg and anti HBc serum levels.

The effect of postfusion cell density on establishment of hybridomas.

The effect of postfusion cell density on establishment of hybridomas in primary microculture was studied. Following fusion of BALB/c spleen and NS0 myeloma cells in the ratio of 5:1 we demonstrated that seeding the cells at a concentration of about 20-25 X 10(4) spleen cells per well resulted in maximal number of wells containing only one growing hybridoma clone (40.1-43.