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Biomedical subjects

B Wahren

Publications and source records attributed to B Wahren.

At least 253 records · Page 14Linked to original sources
PubMed1989

Fine specificity of IgG subclass response to group antigens in HIV-1-infected patients.

There is an association between the clinical stage of HIV-1 infection and the presence of antibodies against viral gag proteins (p17 and p24). The IgG subclass (G1 and G3) pattern against these antigens was analysed in stable patients and HIV patients progressing to AIDS. Antibodies were analysed with whole viral or peptide ELISA (using sequentially overlapping peptides) and Western Blots. IgG1 was found to be the dominant anti-HIV-1 IgG subclass and IgG1 antibodies declined in progressing patients against all HIV antigens evaluated in Western blot, including p17, p24, p31, gp41, p64, gp120 and gp160. In contrast IgG3 antibodies, which were found to be predominantly directed against gag proteins, and which could be detected in almost all patients, remained in the circulation during disease progression. By peptide assays distinct immunogenic regions were found in p17 in contrast to more evenly distributed epitopes in p24. A decreased divergence of antibody reactivity to both p17 and p24 peptides in the group of patients who developed AIDS was seen. No reaction to any single gag epitope related to disease progression. The difference between IgG1 and IgG3 anti-gag antibodies in relation to clearance during disease progression may depend on different properties of immune complexes formed by these two IgG subclasses.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Use of synthetic oligopeptides in identification and characterization of immunological functions in the amino acid sequence of the envelope protein of HIV-1.

Following computer-assisted analysis of the amino acid sequence of various HIV-1 isolates, we synthesized a series of oligopeptides derived from variable and conserved regions of the envelope protein complex gp120/gp41. The peptides were used in ELISA tests for their reactivity with human antisera from HIV-1 positive individuals; patients with clinically manifested AIDS showed only a rather limited reaction, predominantly with two peptides (p102-112, p316-326), which is in contrast to sera from HIV-1 positive asymptomatic individuals, whose sera were reactive with almost all peptides. Using consecutive sera of the same patients, decreasing antibody titers to defined epitopes could be shown to occur during the development of AIDS. Cellular immune response recognition was analyzed in T-cell proliferation assays by [3H]thymidine incorporation. One peptide localized in a conserved region clearly induced proliferation of T-cells. Those data were combined to a map of the functions localized in the various regions of the HIV-1 envelope proteins.

Acquired Immunodeficiency Syndrome↗
PubMed1989

HIV-1 peptides induce a proliferative response in lymphocytes from infected persons.

In a comprehensive search for T-cell epitopes of HIV-1, several new regions were discovered. The analysis was performed with lymphocytes of HIV-1-infected persons in various stages of the infection. Peptides covering the entire group antigen (gag), and transmembrane (gp41) regions, and one-half of envelope (gp120) regions of HTLV-IIIB were studied. Both common and patient-unique responses were identified. Twelve common gag T-cell sites were discovered, as well as patient-unique activating peptides. The gag peptides elicited the most frequent cell responses and the responses remained in late stages of disease. Only 1 of the 12 T-cell activating gag peptides was reactive with specific anti-HIV IgG. Eighteen common env-representing peptides evoked T-cell responses. They could be grouped into four previously undescribed regions of gp120 and two known sites, the hypervariable stretch and part of the CD4 binding region. Cell responses to env peptides were common in early stages of disease and tended to decrease in ARC and AIDS. The gp41-representing peptides evoked a cellular response to a region close to the N-terminus of the hydrophobic transmembrane region. In addition to the T-cell activating peptides, peptides representing p15 and p19 as well as previously recognized regions of gp120 and gp41 appeared to be potent B-cell epitopes.

AIDS-Related Complex↗
PubMed1988

Tumor markers carcinoembryonic antigen, CA 50, and CA 19-9 and squamous cell carcinoma of the esophagus. Pretreatment screening.

Pretreatment serum levels of the tumor markers carcinoembryonic antigen (CEA), CA 50, and CA 19-9 in 95 patients with squamous cell carcinoma of the esophagus and 32 age-matched controls were compared. Thirty-nine percent of the cancer patients showed elevated (greater than or equal to 5 micrograms/l) serum CEA levels, 41% had elevated (greater than or equal to 17 U/ml) CA 50 levels, and 13% showed elevated (greater than or equal to 37 U/ml) CA 19-9 levels. The tumor markers showed a considerable degree of complementarity, and combined tumor marker analysis increased the sensitivity to 59%. Raised CEA levels were found significantly more frequently in intrathoracically localized tumors than in cervical cancers. Patients surviving less than 6 months showed a higher rate of elevated CEA assays than those who survived 6 to 18 months. No certain correlation was established between tumor marker elevation and tumor stage or tumor differentiation.

Antigens, Neoplasm↗
PubMed1988

Tumor markers carbohydrate antigens CA 19-9 and CA-50 and carcinoembryonic antigen in pancreatic cancer and benign diseases of the pancreatobiliary tract.

Sera from patients with diseases in the pancreas, gallbladder, and bile duct were analyzed for the tumor markers CA 19-9, CA-50, and carcinoembryonic antigen. In particular CA 19-9 and CA-50 appear to be valuable in differentiating malignant from benign disease in these organs. Our sample of 72 patients with pancreatic cancer also indicates that CA 19-9 and CA-50 complement each other in 21% of the cases. They are also shown to be reliable for monitoring disease: following radical surgery for pancreatic cancer low levels of CA 19-9 and CA-50 were noted, while progressive rises of these tumor markers were related to disease progression.

Antigens, Neoplasm↗
PubMed1988

Elevated antibody titers against cytomegalovirus among patients with testicular cancer.

The epidemiology of testicular cancer (TC) has 2 distinguishing features. First, it has an unusual unimodal age-incidence curve which peaks about age 30, and decreases with increasing age. Second, risk of the disease has been consistently associated with a high standard of living inasmuch as it is a disease of young white men of generally higher social class in economically developed populations. These features suggest that risk may be related to relatively late age of exposure to common infectious agents resulting in damage to the developing testis. We evaluated this hypothesis in a serologic case-control study in which subjects were compared for both prevalence and level of antibody to the following agents: measles, mumps, rubella, varicella (VZV), herpes simplex (HSV), cytomegalovirus (CMV), toxoplasmosis, Chlamydia, and Mycoplasma hominis. The TC cases included 50 with seminoma, 50 with embryonal carcinoma, and 17 with other sub-classifications. There were 100 male controls of comparable age. No consistent differences were found for any of the non-herpes viruses. For VZV, cases generally had elevated titers, significantly so for the seminoma patients, relative risk (RR) = 6.3 (95% confidence interval, 3.0-13.3) adjusted for the titer distributions of HSV and CMV. For HSV, seminoma patients also had elevated titers, RR = 2.6 (1.0-6.4). The strongest association was with CMV. Patients had a higher prevalence rate than controls, RR = 2.0 (1.1-3.6), and a gradient of risk with titer level. Overall, those in the highest titer quartile had an RR of 4.9 compared to those with no antibody, with a significant trend (p = 0.0002). Since age at CMV infection is directly related to social class, these findings suggest that delayed exposure to CMV, resulting in a more severe infection, may be related to risk of TC. However, confounding by immune status of the cases or by other risk factors of TC could not be evaluated and may account for this observation.

Antibodies, Viral↗
PubMed1988

IgG subclass reactivity against human immunodeficiency virus (HIV) and cytomegalovirus in cerebrospinal fluid and serum from HIV-infected patients.

Cerebrospinal fluid (CSF) and serum samples from 17 patients seropositive for the human immunodeficiency virus (HIV) were analysed for specific IgG1-4 against HIV and cytomegalovirus (CMV). Measles IgG was studied as a reference to detect blood-brain barrier (BBB) defects. All patients had IgG1 antibodies against HIV in both CSF and serum, and all had CMV IgG1 in serum (16 in CSF). Anti-HIV IgG was synthesised intrathecally in 11 patients, IgG3 in three patients, and IgG4 in three patients. Intrathecal production of anti-CMV IgG1 was found in three patients, IgG2 in one, IgG3 in three, and IgG4 in one. Intrathecal anti-HIV IgG synthesis could be demonstrated in all stages of the disease. Analysis of all IgG subclasses allowed intrathecal HIV and/or IgG production to be detected also in patients in whom intrathecally synthesised IgG was restricted to IgG2, 3, or 4. The expression of HIV-specific IgG subclasses in CSF and serum was more restricted in AIDS patients than in HIV-infected persons without clinical AIDS. On the contrary, the largest number of CMV-specific IgG subclasses was found in AIDS patients. Intrathecal HIV or CMV IgG subclass production was seen both with and without neurological symptoms. The peripheral T4 cell counts were not obviously related to neurological symptoms. Even patients with low peripheral T4 cell counts had evidence of intrathecal antibody synthesis against HIV and sometimes CMV, suggesting a retained helper function of T cells in the central nervous system.

AIDS-Related Complex↗
PubMed1988

Profiles of epitope-defined markers in sera from patients with testicular germ cell tumors.

Epitope-defined tumor markers of AFP (FA), HCG (PM), PLAP (H7) and CEA (D/AH) were determined by monoclonal antibodies in sera of patients with germ cell tumors of the testis. Characteristic profiles of PLAP (H7) were seen in localized and metastatic seminoma and in sera of patients with mixed tumors with seminoma components. PLAP (H7) levels started to rise 10 months before clinical detection of recurrence in one case. Persisting elevated levels of PLAP (H7) in several cases were indicative of metastatic seminoma. PLAP (H7) occurred rarely in sera of patients with metastasing non-seminomatous tumors. AFP (FA) detected in seminoma sera led to identification of non-seminomatous disease in one case. High AFP (FA) alone occurred in yolk sac tumors, HCG (PM) with AFP (FA) or PLAP (H7) in patients where the tumors had components of teratoma and/or embryonal carcinoma, moderately elevated levels of AFP (FA) and sometimes also HCG (PM) occurred.

Alkaline Phosphatase↗
PubMed1988

Specific IgG subclass reactivity in herpes simplex encephalitis.

Serum and cerebrospinal fluid (CSF) samples from 19 patients with a previous diagnosis of herpes simplex virus encephalitis (HSVE), from 14 patients with a previous diagnosis of non HSVE encephalitis and from 21 healthy subjects were examined to detect IgG subclasses 1-4 reactive with herpes simplex virus (HSV), cytomegalovirus (CMV) and varicella zoster virus (VZV). Antibodies to HSV were detected in CSF and serum from the 14 HSVE-patients with a reactivated HSV infection and from 3 of the 5 patients with a primary HSV infection. The predominant subclass pattern was an early HSV-specific IgG1 rise, followed by IgG3 and, more seldom, IgG4; HSV IgG2 was rarely seen. In HSVE patients, HSV IgG3 was absent in early samples and usually appeared 10-20 days after onset of disease. In 14 out of 16 seropositive healthy controls, on the other hand, HSV IgG3 was present in the CSF. Rising VZV IgG levels in serum and CSF were found in 11 HSVE patients. Eight of them showed signs of intrathecal VZV IgG1 synthesis. The VZV IgG reactivity was restricted to IgG1 in 7 of these whereas the HSV IgG subclass response also included IgG3 or 4. The appearance of several HSV IgG subclasses appeared to serve as a marker of HSV infection in spite of the serological VZV reaction, usually restricted to VZV IgG1. Intrathecal synthesis of the quantitatively minor HSV IgG3 and 4 subclasses was detected earlier than intrathecal synthesis of total HSV IgG, dominated by IgG1 in 4 patients with HSVE.

Encephalitis↗
PubMed1988

IgG antibodies to human herpesvirus-6 in children and adults and in primary Epstein-Barr virus infections and cytomegalovirus infections [corrected].

Antibody titers against human herpesvirus-6 (HHV-6) were determined in 80 healthy adults and 100 children and teenagers from Sweden to gain information on the role of the virus and its epidemiology. Based on a positive immunofluorescence titer of 1:10 and above, about 85% of the adults and children were seropositive with 60% seropositivity of children below age one year. Titers were generally higher in patients with simultaneous EBV or CMV infection, yet crossreactivity appeared essentially no problem. HHV-6 thus is ubiquitous like other herpesviruses. Primary infection seems to occur early in life, and reactivation or delayed primary infection may be associated with a variety of disorders.

Adolescent↗
PubMed1988

Acid hydrolysis of serum samples to increase detection of HIV antigen.

Sera from 32 HIV-infected patients and 20 controls were assayed for HIV antigen (HIV-Ag) and antibodies following acid hydrolysis. Acid hydrolysis, followed by neutralization immediately prior to the assay, was found to be a simple means to solubilize immune complexes and allowed recovery of 40-50% of complexed antigen. Following acid hydrolysis, HIV-Ag levels rose or became detectable in 22/32 patients and HIV IgG1-4 levels rose in 17/20 patients studied. The results show that complexed HIV-Ag may evade detection in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Combination ELISAs for antiviral antibodies in CSF and serum in patients with neurological symptoms and in healthy controls.

A combination enzyme-linked immunosorbent assay (ELISA) was designed to improve the estimation of serum: cerebrospinal fluid (CSF) antiviral IgG ratios. Microplate wells were coated with five different virus antigens. Serum and CSF from 66 patients referred for CSF serology and from 21 healthy controls were studied. In a comparison with serum: CSF IgG titre ratios, absorbance ratios were found to be suitable for the evaluation of intrathecal antiviral IgG synthesis. A slight blood-brain barrier (BBB) disturbance affected only the passage of albumin over the BBB, whereas a more pronounced BBB defect resulted in increased IgG levels in the CSF. Intrathecal antiviral IgG synthesis was demonstrated in 15 patients with viral CNS infections or inflammatory diseases. Very high serum: CSF antiviral IgG titre ratios and absorbance ratios, found in six patients, were interpreted as signs of diminished IgG passage over the BBB due to impaired CSF circulation.

Adult↗
PubMed1988

B and T cell reactivities after immunization of macaques with HIV subcomponents.

A model system was established for studies of humoral and cellular immunity to human immunodeficiency virus (HIV) antigens after vaccination. Macaques (Macaca fascicularis) were immunized with purified HIV, an infected cell extract rich in gp120 or polypeptides of cloned genes representing parts of p24, gp41, and gp120. Western blot analysis best showed the appearance of antibodies to nucleocapsid proteins, and antibodies to higher molecular weight envelope glycoproteins were better demonstrated by radioimmunoprecipitation. With whole HIV, antibodies to p24 appeared first, and sometimes were the only ones to be demonstrable. Several immunizations with HIV or recombinant polypeptides were required to obtain antibodies to gp120, and the responses were weak. Although the envelope-specific response was weak, this was the only component that mediated neutralizing capacity. Escherichia coli-derived viral transmembrane polypeptide (g)p41 also had a poor immunizing effect. IgG synthesis from B cells in vitro was demonstrable to antigens and generally paralleled the antibody titers of sera after multiple immunizations. The HIV-specific lymphocyte proliferation response as measured by DNA synthesis was best seen with polypeptide p24-15, followed by the other antigens.

Animals↗
PubMed1988

Clinical effects of monoclonal antibodies (MAb 17-1A) in patients with metastatic colorectal carcinomas.

Ten patients with metastatic colorectal carcinoma were treated with MAb 17-1A (IgG2A). Before infusion, MAb was incubated in vitro with isolated autologous blood mononuclear cells. Treatment was given in repeated courses (2-4 times) to a maximum dose of 1000 mg of MAb 17-1A. One patient achieved a clinical complete remission, two patients had a minor response and one patient had stable disease for 5 months. The median survival for the four responders was 19 months compared to 7 months for the six non-responders. Therapy was well tolerated. In this series, 32 infusions of MAb 17-1A were given. The serum half-life of MAb 17-1A was approximately 22 hours. All patients developed anti-mouse antibodies of both IgG and IgM classes. No relation between adverse reactions and anti-mouse antibodies was seen. At 3 occasions allergic reactions were noted. Skin test with MAb 17-1A seems to reliably predict for allergic reactions.

Adult↗
PubMed1988

Antiherpesvirus activity and mechanism of action of indolo-(2,3-b)quinoxaline and analogs.

The antiherpesvirus activity of 14 derivatives of indoloquinoxaline was tested. The most active was 2,3-dimethyl(dimethylaminoethyl)5H-indolo-(2,3-b)quinoxaline, also called B-220. The antiherpesvirus mechanism of B-220 was sought. The compound inhibited replication of herpes simplex virus type 1, cytomegalovirus, and varicella-zoster virus in tissue culture at concentrations of 1 to 5 microM, depending on the cell type used for assay and the amount of virus. Cellular toxicity was seen at a concentration of 10 to 30 microM, and antiviral activity in the human bladder cancer and human embryonic lung fibroblast cell lines tested was found at concentrations 3 to 15 times lower than the concentrations causing cellular toxicity. Viral DNA synthesis, as well as production of early and late viral proteins, was inhibited at 0.5 to 4.5 microM B-220, but viral DNA polymerases tested in vitro were not inhibited at these concentrations. There was no interaction with the pyrophosphate analog foscarnet, and no reversal of the antiviral activity of B-220 occurred with naturally occurring nucleosides. We conclude that the antiviral effect depends on the multiplicity of infection and may occur at the level of viral DNA synthesis and that no interference occurs with pyrophosphate analogs or nucleosides. The more potent activity against viral DNA than against cellular DNA may be caused by a true selectivity for herpesvirus DNA or by the higher metabolism of viral DNA in infected cells.

Acyclovir↗
PubMed1988

Inhibition of varicella-zoster virus-induced DNA polymerase by a new guanosine analog, 9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine triphosphate.

The triphosphates of the antiherpesvirus acyclic guanosine analogs 9-[4-hydroxy-2(hydroxymethyl)butyl] guanine (2HM-HBG), 9-(2-hydroxyethoxymethyl)guanine (acyclovir [ACV]), and 9-(3,4-dihydroxybutyl)guanine (buciclovir) were examined for their effects on partially purified varicella-zoster virus (VZV) DNA polymerase as well as cellular DNA polymerase alpha. The triphosphate of 2HM-HBG competitively inhibited the incorporation of dGMP into DNA catalyzed by the VZV DNA polymerase. 2HM-HBG-triphosphate (2HM-HBG-TP) had a higher affinity for the dGTP-binding site on the VZV DNA polymerase than did dGTP; apparent Km and Ki values of dGTP and 2HM-HBG-TP were 0.64 and 0.034 microM, respectively. ACV-triphosphate (ACV-TP) was found to be the most potent inhibitor of VZV DNA polymerase. ACV-TP had a 14 and 464 times better direct inhibitory effect than 2HM-HBG-TP and buciclovir-triphosphate, respectively. The cellular (human embryonic lung fibroblast) DNA polymerase alpha inhibition was related to viral polymerase inhibition as efficacy ratios: 2HM-HBG-TP had a ratio of more than 1,000, which appeared to be similar to that of ACV-TP.

Acyclovir↗
PubMed1988

Lymphocyte and IgG responses to different herpes simplex virus antigens in patients with frequent HSV-1 reactivations.

Seventeen patients with a history of frequent clinical herpes simplex (HSV) reactivations and 13 HSV seropositive controls were monitored for 6 months. The patients had 4-8 clinical reactivations during the study. No clinical HSV reactivations were observed in the controls. IgG subclasses directed against HSV-1 nucleocapsid, membrane and glycoprotein C (gC) antigens were determined after the study period. Anti-HSV IgG4 directed against gC was found more often in the patients (65%) than in the controls (8%, P less than 0.025). The same trend was seen for IgG4 against HSV nucleocapsid antigen (88 and 46%, n.s.) and HSV membrane antigen (82 and 38%, n.s.). In both patients and controls IgG3 was found more often against nucleocapsid antigen compared to membrane or gC antigens (P less than 0.001). Lymphocytes were stimulated with the different antigens and the anti-HSV IgG subclass responses and cellular proliferation were determined. Lymphocyte produced IgG4 against HSV nucleocapsid antigen was found more often in patients than in controls (47 and 8%, P = 0.05) and membrane antigen (41 and 0%; P less than 0.025). No differences were found in the magnitude of lymphocyte proliferation responses between patients and controls. Lymphocyte proliferation responses were stronger to nucleocapsid antigen than to membrane or gC antigens (P less than 0.01).

Adult↗