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Biomedical subjects

K C Chadha

Publications and source records attributed to K C Chadha.

At least 37 records · Page 2Linked to original sources
PubMed1989

Interferon and interferon inhibitor levels in patients infected with varicella-zoster virus, acquired immunodeficiency syndrome, acquired immunodeficiency syndrome-related complex, or Kaposi's sarcoma, and in normal individuals.

PURPOSE: Previous studies had reported that normal individuals do not have measurable levels of interferons in their circulation, whereas high levels have been found in patients in the early stages of AIDS (acquired immunodeficiency syndrome) and in those with AIDS-related complex (ARC). This study was undertaken to compare levels of interferon and interferon inhibitors in plasma samples from patients with AIDS, ARC, Kaposi's sarcoma, or varicella-zoster virus infection, and from control subjects. PATIENTS AND METHODS: A total of 206 persons were tested for the presence of interferon and interferon inhibitors in their plasma: 76 with ARC or AIDS, with or without Kaposi's sarcoma or lymphoma; 32 with varicella-zoster infection; 12 with AIDS-unrelated Kaposi's sarcoma; and 86 normal control subjects at high or low risk of AIDS with or without positive antibody levels to human immunodeficiency virus-1. Total interferon activity was measured by bioassay and the subtypes were not separated. RESULTS: Of 86 normal control subjects, 85 had no significant levels of interferon or interferon inhibitor. One disease-free homosexual exhibited measurable interferon levels. Patients acutely infected with varicella-zoster virus showed no measurable interferon or inhibitor levels except if they were in a high-risk group for AIDS. Seventy-six patients with ARC or AIDS exhibited measurable circulating interferon levels. Only patients with AIDS had interferon inhibitors in their circulation. Of 12 patients with Kaposi's sarcoma unrelated to AIDS, none had measurable interferon inhibitor levels, but some exhibited measurable interferon levels. CONCLUSION: It is suggested that levels of interferon inhibitor should be considered when interferon is used therapeutically in viral or neoplastic diseases.

AIDS-Related Complex↗
PubMed1986

Interferon inactivator(s) in patients with AIDS and AIDS-unrelated Kaposi's sarcoma.

Interferon inhibitory activity was found in the plasma of 11 of 14 patients with the acquired immune deficiency syndrome (AIDS). This was not seen in 75 normal persons, including six whose specimens were randomly and blindly interspersed among the patient samples. Plasma from a single patient with the AIDS prodrome (AIDS-related complex), who later demonstrated AIDS, did not contain interferon inhibitors but did contain high levels of interferon. Three patients with AIDS-unrelated Kaposi's sarcoma had neither significant levels of interferon nor interferon inhibitory activity. The existence of interferon inhibitory activity in the plasma has to be taken into account when interferon preparations are administered therapeutically.

AIDS-Related Complex↗
PubMed1986

Modulation of the interferon antiviral activity by adriamycin in human cells in culture.

The antiviral activity of exogenously applied HuIFN-alpha was significantly reduced in cells pretreated with non-toxic concentrations of adriamycin. With low concentrations of adriamycin (up to 0.125 micrograms/ml) the effect was reversible in all cells tested. In human foreskin (BG-9) cells, that are more resistant to adriamycin toxicity, higher nontoxic concentrations of adriamycin (0.625 micrograms/ml) caused an irreversible decrease in sensitivity to HuIFN-alpha. Under these conditions, adriamycin pretreatment irreversibly inhibited the rate of cellular protein synthesis in BG-9 cells by about 30%. In contrast, cellular RNA synthesis was inhibited by 80% in 4 h after exposure to the drug, but was restored to almost normal levels (97% of control) at day 4 after removal of the drug. These results suggest that the loss of sensitivity of adriamycin-treated BG-9 cells to HuIFN-alpha may be related to the inhibition of cellular protein synthesis.

2',5'-Oligoadenylate Synthetase↗
PubMed1986

Characterization of non-T effector cell subpopulations involved in production of human alpha interferon.

The phenotype of the human effector leukocyte subset involved in production of alpha interferon was examined using positive and negative selection techniques including murine monoclonal antibodies. The data suggest that the effector cell responsible for the elaboration of human alpha interferon is surface immunoglobulin positive, lacks either the E-rosette receptor or any monocyte determinants and is also negative for expression of the surface antigens identified by Leu-10 and Leu-11b monoclonal antibodies. Neither monocytes nor polymorphonuclear leukocytes were shown to play a role in regulation or production of alpha interferon. The data further imply, however, that the Leu-7+, large granular lymphocyte subpopulation may play a critical role in regulating human alpha interferon production by surface immunoglobulin positive B cell effectors.

Antibodies, Monoclonal↗
PubMed1986

Regulation of in vitro human leukocyte interferon production: effect of prostaglandin synthetase and phosphodiesterase inhibition.

A great variability exists in the in vitro capability of peripheral blood leukocytes (PBL) of apparently healthy adults to produce IFN-alpha. In this report, we have studied the effects of prostaglandins, indomethacin and pentoxifylline upon IFN-alpha production by the PBL of normal healthy donors. The donors were divided into two groups: "normal producers" - donors that consistently produced greater than 2,000 ref. units IFN-alpha per 10(7) PBL and "low producers" - donors that consistently produced less than 2,000 ref. units IFN-alpha per 10(7) PBL. Addition of exogenous PGE1 or PGE2 into interferon production media significantly inhibited IFN-alpha yield by the PBL of both normal and low producers. The inhibition was dose dependent. A significant rise in the IFN-alpha yield was seen when PBL of "low producers" were exposed individually to either pentoxifylline or indomethacin. However, no increase in titer of IFN-alpha was seen when PBL of "normal producers" were exposed to either of these two agents during interferon production periods. With regard to PBL of "low producers", the enhancement of IFN-alpha yield was further potentiated when both indomethacin and pentoxifylline were utilized concurrently at their optimal concentrations. These results suggest that enhancement of IFN-alpha production by PBL of apparently healthy adults who are low producers may be possible and may have preventive value.

Alprostadil↗
PubMed1985

Calmodulin in interferon preparations: effect of interferon on calmodulin bioactivity.

Heat-stable calmodulin immunoreactivity and bioactivity were detected in crude preparations of various types of human, murine and chicken interferons (IFNs). Calmodulin containing HuIFN-alpha was retained on a trifluorophenothiazine-Sepharose column. The two activities were separated by serial elutions with 50 microM Ca2+ (HuIFN-alpha) followed by 2 mM EGTA (calmodulin). While maintaining its full antiviral activity, calmodulin free HuIFN-alpha inhibited enhancement of Ca2+-ATPase activity in vitro by authentic purified eukaryote calmodulin. These results indicate that IFNs are calmodulin-binding proteins and that the secretion of both IFNs and calmodulin occurs from IFN-induced cells.

Animals↗
PubMed1984

The effect of malignant epithelial tumors, surgical therapy, and bacterial sepsis upon various parameters of interferon system.

The influence of tumor load, surgical trauma, and bacterial sepsis upon the ability of patient's peripheral leukocytes to produce interferon-alpha (IFN-alpha), the detectable serum IFN levels and circulating serum IFN inactivators were studied. Peripheral blood leukocytes of patients with solid tumors had significantly reduced ability to produce IFN-alpha. Complete resectional surgery resulted in restoration of their ability to produce normal IFN-alpha levels. Circulating IFN levels were detectable in 70% of patients with localized disease while only in 20% of patients with metastatic disease. Interferon-alpha activators were detected in 45% of all patients. Both circulating interferon and IFN-alpha inactivators became undetectable upon tumor resection. Surgical trauma is accompanied by a transient but definite decrease in IFN-alpha production capability. Bacterial sepsis during postoperative days, in patients who successfully recovered, was definitely accompanied by increase in IFN-alpha production capability. Our findings suggest that advanced malignant epithelial tumors have an adverse effect upon the patient's ability to produce interferon and are often accompanied by the presence of circulating serum interferon inactivators. These effects can be reversed by surgical resection of the malignant neoplasm.

Adult↗
PubMed1984

Interferon and interferon inactivators in patients with acquired immune deficiency syndrome and Kaposi's sarcoma. A preliminary report.

The interferon system has been implicated in the diagnosis and potential treatment of acquired immune deficiency syndrome (AIDS). In our study of AIDS patients we have identified the presence of circulating serum interferon inactivator(s). These interferon inactivators were not detected in AIDS prodrome patients or in patients with classical Kaposi's sarcoma. The evidence suggests that interferon inactivators may play a role in the clinical manifestation of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Antiviral and antiproliferative activities of three molecular components of leukocyte-derived human interferon.

Antiviral and antiproliferative activities of three naturally occurring components of leukocyte-derived human interferon (HuIFN-alpha) separated by concanavalin A-agarose affinity chromatography were studied in a variety of neoplastic cell lines. Significant differences were seen with these different components. The results strongly suggest that careful consideration must be given while selecting any one component of HuIFN-alpha for any of the antiviral or antiproliferative studies. There is no clear evidence that glycosylation of HuIFN-alpha has any significant influence on its in vitro antiviral or antiproliferative activities, although apparently glycosylated and non-glycosylated components gave different antiviral and antiproliferative responses in different tumor cells.

Cell Division↗
PubMed1982

Adsorption of human alpha (leukocyte) interferon on glass: contributions of electrostatic and hydrophobic forces.

Human leukocyte-derived interferon (HuIFN-alpha) can be displaced from controlled-pore glass (CPG) with alkylamines at 0.1-0.3 M concentration. The eluting power of an alkylamine correlates positively with the extent of its alkylation: CH3NH3 + less than (CH3)2NH2 + less than (CH3)3NH+ less than (CH3)4N+. Interferon can also be recovered using an electrolyte and ethylene glycol as cosolvents. Apparently, both hydrophobic and electrostatic forces are involved in the adsorption of HuIFN-alpha to CPG.

Adsorption↗
PubMed1982

Interferon system of human cornea cells: interferon production, characterization, and development of antiviral state.

The interferon (IFN) system of human cornea cells in culture was studied. IFN produced by these cells by infection with Newcastle disease virus (NDV) was shown, by neutralization studies with specific antisera against human alpha interferon (HuIFN-alpha) and human beta interferon (HuIFN-beta), to contain 90-95% antiviral activity characteristic of the HuIFN-beta and 5-10% that of HuIFN-alpha. The chromatographic behavior of human cornea IFN on Con A-Sepharose and zinc chelate agarose columns was identical to that of HuIFN-beta produced by human foreskin cells. The cornea cells developed marked resistance when exposed to either HuIFN-beta or human gamma interferon (HuIFN-gamma) against vesicular stomatitis virus (VSV), but to a much lesser degree against HSV-1. Both the laboratory-adapted strain and a clinical isolate of HSV-1 were found to be resistant to HuIFN-beta and HuIFN-gamma as compared with VSV. The clinical isolate of HSV-1 was, however, more sensitive to HuIFN-gamma than the laboratory-adapted strain. Furthermore, a combination of HuIFN-beta and HuIFN-gamma did not significantly increase the level of antiviral state induced in cornea cells against HSV-1. These results suggest that in-vitro culture of human cornea cells can be a valuable system to evaluate the potential of chemotherapeutic agents against common ophthalmic viral infections.

Cells, Cultured↗
PubMed1982

Effects of source leukocyte collection on the immune system.

This study was initiated in order to assess any immunologic effects that source leukocyte concentrate collection might have on double-bag plasmapheresis donors. Previous studies have shown that surveillance parameters, such as T versus non-T lymphocyte subpopulations, showed no abnormal values in donors with as many as 500 visits over a 12-year period. The present study demonstrates that the frequency and the total number of leukocyte donations do not effect the lymphocyte subpopulations and functions observed. No significant changes were noted for specific and nonspecific stimulation, natural killer (NK) cell activity, lymphocyte surface markers and a variety of functional parameters. For example, the apheresis donors manifested no differences in NK cell activity, human leukocyte interferon production, IgG synthesis by B cells and percent suppression of both IgG synthesis and mixed lymphocyte cultures, when compared to non-apheresed donors.

Blood Donors↗
PubMed1981

Chromatography of human leukocyte interferon on controlled pore glass.

Human leukocyte interferon (HuIFN-alpha ) was adsorbed on controlled pore glass (CPG) beads in 0.01 M potassium phosphate, pH 7.2. Partial recovery fo HuIFN-alpha from CPG, ranging from 50% to 75%, was obtained with ethylene glycol (6.8 M), ammonium chloride (1.0 M) and Tris.HCl (1.0 M). A near complete recovery (90%) was obtained with potassium phosphate (1 M), but there was no selectivity in the elution vis á vis other proteins. An efficient elution of HuIFN-alpha was accomplished with tetramethyl-, and tetraethylammonium chlorides: the recovery of HuIFN-alpha was complete at low concentrations (0.25 M to 0.50 M) of these salts at pH 8.0 and the elution of interferon was more selective than with other eluants.

Ammonium Chloride↗
PubMed1981

Inhibition of cellular and virus-associated nucleotide polymerases by, and anti-herpes simplex virus activity of, streptovaricin derivatives.

Fourteen streptovaricin derivatives were tested for inhibition of cellular nucleotide polymerases (deoxyribonucleic acid polymerases alpha, beta, and gamma, terminal deoxynucleotidyltransferase [TdT], and ribonucleic acid polymerase II), simian sarcoma virus deoxyribonucleic acid polymerase, and herpes simplex virus type 1-induced deoxyribonucleic acid polymerase (HSV-DP). Three compounds (strep-tovadienal C, prestreptovarone, and streptoval Fc) preferentially inhibited TdT and HSV-DP over the other enzymes. These compounds inhibited HSV-DP more potently than they inhibited TdT. Evidence indicated that the mode of inhibition of TdT and HSV-DP by streptovadienal C and prestreptovarone was by interaction with the enzymes and not with template-primer, initiator, substrates, or divalent cations required for enzyme activity. Furthermore, data suggested that these compounds bind with greater affinity to HSV-DP than to TdT. Streptovadienal C and prestreptovarone were examined for their effect on the replication of herpes simplex virus type 1 in African green monkey kidney (CV1) cells. These compounds produced 2- and 3-log drops in virus titer, respectively, at concentrations not significantly affecting cell viability. This correlated with evidence indicating a greater binding affinity of these compounds for HSV-DP over cellular nucleotide polymerases.

Animals↗