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G Bratt

Publications and source records attributed to G Bratt.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cellular cytotoxic response induced by DNA vaccination in HIV-1-infected patients.

BACKGROUND: DNA vaccination is known to generate immune responses against HIV-1 in animal models. We aimed to assess the efficacy of DNA vaccination in induction of immune responses in HIV-1-infected human beings. METHODS: Nine symptom-free HIV-1-infected patients were immunised with DNA constructs encoding the nef, rev, or tat regulatory genes of HIV-1. The patients were selected for having no or low antibody reactivities to these antigens. HIV-1-specific cytotoxic T-lymphocytes (CTLs), precursor frequencies, and antigen-specific proliferative responses were measured before, during, and after three immunisations over 6 months. FINDINGS: Cellular immune reactivities against the HIV-1 regulatory proteins were absent or low before DNA immunisation. DNA vaccination induced detectable memory cells in all patients and specific cytotoxicity in eight patients. CTLs were MHC-class-I restricted and mainly of CD8+ origin. In three patients the cellular activity was transient, decreasing after an initial response. INTERPRETATION: DNA immunisation with HIV-1 genes can induce specific cellular responses in human beings with no apparent side-effects. It is theoretically possible that HIV-1-specific cytotoxic responses to regulatory proteins could lead to infected cells being eliminated before they have released new viral particles. However, it is possible that the patients we selected responded less than would non-selected or non-infected individuals. The small number of patients presented here does not allow generalisation of our findings.

AIDS Vaccines↗
PubMed1998

Induction of specific T-cell responses in HIV infection.

OBJECTIVES: To induce recovery of HIV-1-specific immune responses by combining immunization with antiviral chemotherapy. DESIGN: Forty HIV-infected patients entered a double-blind study with recombinant gp160 in combination with zidovudine or placebo. The pretreatment observation period was around 2 years and the treatment period 5 years. Eighty matched HIV-infected patients served as controls. METHODS: Immune status was monitored by proliferation assays with HIV-specific antigens, mitogens and recall antigens. Viral load, CD4 cell counts, apoptosis, T-cell clonal analysis and CC-chemokine receptor (CCR)-5 status were determined. RESULTS: All immunized patients showed a strong and HIV-specific T-cell proliferative response. This response was related to the immunizations, and was not enhanced by the zidovudine monochemotherapy given during the first 6 months of the immunizations. The treatments did not significantly alter viral load. Potent antiviral combination therapy given to non-immunized individuals reduced their viral load but did not influence HIV-specific immune responses. There was a trend for an increased frequency of non-progression in the immunized group compared with controls. These individuals had both wild-type and mutant CCR-5 genes. CONCLUSION: The results clearly show that restoration of HIV-specific T-cell immunity occurs after immunization with the HIV gp160 antigen and is not influenced by the addition of antiviral monochemotherapy. Even intensive chemotherapy alone did not restore HIV-specific immunity and immunization alone did not influence viral load. This suggests that combinations of intensive chemotherapy with specific HIV immunization would result both in viral load reduction and improved immune responses to HIV.

AIDS Vaccines↗
PubMed1997

N-acetylcysteine treatment and the risk of toxic reactions to trimethoprim-sulphamethoxazole in primary Pneumocystis carinii prophylaxis in HIV-infected patients.

In a randomized double blind placebo controlled trial, HIV sero-positive patients with CD4+ cell count less than 200 x 10(6)/l or an AIDS diagnosis were evaluated for drug reactions to trimethoprim-sulphamethoxazole (TMP-SMX) during treatment, including pretreatment, with N-acetylcysteine (NAC) 800 mg daily or placebo. TMP-SMX (one double-strength tablet containing 160 mg of trimethoprim and 800 mg of sulphamethoxazole) was given three times weekly as primary Pneumocystis carinii (PCP) prophylaxis. Thirty percent (n = 15) of the patients experienced adverse reactions 8-20 (mean 12.7) days after starting with TMP-SMX. At entry, low cysteine and glutathione levels in plasma were found in the HIV-positive patients. Age, sex, CD4+ count, plasma cysteine and glutathione levels were not risk factors for adverse reactions to TMP-SMX. However, concomitant therapy with nucleoside analogues was associated with increased risk for TMP-SMX reactions. Oral NAC 800 mg daily was well tolerated, but replenished neither cysteine nor glutathione levels in plasma. NAC 800 mg/day did not significantly decrease the risk of adverse reactions to TMP-SMX in this study, and could thus not be recommended for this purpose. A prolonged pretreatment period and/or higher dose of NAC may be necessary for clinical effect.

AIDS-Related Opportunistic Infections↗
PubMed1997

The influence of MT-2 tropism on the prognostic implications of the delta32 deletion in the CCR-5 gene.

BACKGROUND: Long-term non-progression in HIV-1-infected patients has been reported to be associated with a 32 base-pair deletion (delta32) in one CCR-5 allele. The normal gene product acts as a coreceptor for HIV cell entry and is essential for infection of cells by non-syncytium-inducing and MT-2-negative HIV-1 strains. METHODS: Forty individuals were studied, all of whom had been HIV-1-seropositive for a mean of 8 years. RESULTS: Eight (20%) were heterozygous for the CCR-5 allele delta32 deletion. Six of these eight patients harboured MT-2-negative HIV-1 strains. Of these six, three were long-term non-progressors with a positive CD4 cell slope, not receiving antiretroviral treatment, whereas the other three were progressors (mean CD4 cell decline, 3.8 x 10(6)/l per month) receiving antiretroviral combination therapy. Two of the eight patients with the delta32 deletion had MT-2-positive HIV-1 strains. Both had very rapid CD4 cell decline (6.7 and 7.6 x 10(6)/l per month, respectively), despite triple antiretroviral therapy including a protease inhibitor. One of the patients with an MT-2-positive virus strain has suffered from Pneumocystis carinii bronchitis and the other from cytomegalovirus colitis. CONCLUSIONS: Disease progression may also occur in individuals with the coreceptor deficiency, especially in association with MT-2-positive HIV-1 strains. It is suggested that MT-2-positive HIV-1 enters cells through the CXC chemokine receptor-4 fusin coreceptor, thus circumventing the defective CC chemokine receptor-5 coreceptor. Various levels of expression of the wild-type CCR-5 gene and the gene with the delta32 deletion might explain variations in the disease progression in heterozygous patients with MT-2-negative HIV-1 strains.

Adult↗
PubMed1996

Analyses of functional antibody responses in HIV-1-infected individuals after vaccination with rgp160.

BACKGROUND: The immune response to HIV infection has been extensively studied and the antibody response against the virus has been characterized in detail. It is, however, still unclear which immune function it is most important to stimulate when administering a vaccine against HIV. OBJECTIVES: To analyze the functional antibody responses in asymptomatic HIV-1-infected individuals after vaccination with rgp160. STUDY DESIGN: Forty-nine asymptomatic HIV-1-infected individuals were followed for 9 months and analyzed for changes in functional antibody responses. Forty of them received HIV-1 envelope rgp160 injections and nine did not. RESULTS: Increased levels of antibodies mediating neutralization and cellular cytotoxicity (ADCC) could be seen in subjects who also showed a better CD4 development compared with the patients without increased levels of functional antibodies. Out of nine matched HIV-infected and influenza-immunized controls, none had increased neutralizing activity and only one had an increased ADCC titer. An increased capacity to block soluble CD4 binding to gp120 occurred in 10 immunized patients. Seroreactivity and avidity maturation were detectable to peptides representing consensus HIV-1 envelope regions, indicating an anamnestic response to the patients own virus. CONCLUSIONS: The humoral immune response in HIV-1-infected individuals was moderately influenced by repeated gp160 immunizations, while previous studies have shown that HIV-specific T-cell reactivity was strongly increased.

Journal Article↗
PubMed1996

An eleven year follow-up of delayed-type hypersensitivity testing for the identification of HIV-1 infected patients at increased risk of developing AIDS.

The objective of this study was to investigate whether testing of delayed-type hypersensitivity (DTH) to recall antigens could be used to identify HIV-1 infected patients at increased risk of death or developing AIDS. Eighty-five HIV-1 infected Swedish homosexual men were tested for DTH using a commercially available kit with 7 recall antigens (Multitest, Mérieux). The patients were followed prospectively for 11 years or until death. The 11-year actuarial progression rate to AIDS was 69% and to death 60%. Older age was identified as a factor predisposing to rapid progression independent of cell-mediated immunity measured by DTH. Patients with a subnormal DTH had a significantly more rapid progression to AIDS and death than did patients with normal DTH, and the time between AIDS diagnosis and death was shorter. For patients with a multiscore (MS) < 10 mm, the median time to AIDS was 59 months, the median time to death 88 months, and the median time from AIDS diagnosis to death 11 months, compared to 106, 139, and 25 months, respectively, for patients with MS > or = 10 mm. Of the individual antigens, only a negative reaction to tuberculin was independently predictive of progression to all 3 endpoints, while a negative reaction to tetanus was independently predictive of progression to death. Thus, determination of DTH improves the early recognition of patients at increased risk of progressive disease.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Continuous detection of CMV DNA in plasma of patients with advanced HIV infection implies the poorest prognosis.

BACKGROUND: The contribution of cytomegalovirus (CMV) to progressive HIV infection is still controversial. OBJECTIVE: The occurrence of CMV DNA in the plasma of patients with advanced HIV infection was studied in relation to the development of clinical disease. STUDY DESIGN: Plasma samples were collected every 2 weeks for 6 months. The patients have thereafter been followed clinically at least every 3 months. CMV DNA was extracted and analysed by a nested PCR. RESULTS: CMV DNA was repeatedly detected in the plasma of five patients for more than 45 days (group 1). These patients also had very low CD4+ cell counts 51+/-41 x 10(6) /l). Three patients in group 1 developed CMV complications and CMV was the cause of death in two cases. Two patients with anti-CMV IgM responses did not develop CMV complications. All five patients died at a mean of 17 months after CMV DNA became continuously detectable by PCR. In another six patients, CMV DNA was not or only sporadically detected (group 2). In these six patients, four are still alive after more than 3.5 years and only one patient developed CMV retinitis 3 years later. CONCLUSIONS: The presence of CMV DNA in plasma was frequent in 11 patients with advanced HIV infection. The continued presence of CMV DNA in plasma of the patients with low CD4+ cell counts was related to the development of clinical CMV disease and carried the poorest prognosis.

Journal Article↗
PubMed1994

Presence of autologous neutralizing antibodies against cytomegalovirus (CMV) in serum of human immunodeficiency virus type 1-infected patients shedding CMV in saliva.

This study evaluated whether cytomegalovirus (CMV) neutralizing capacity affected shedding of CMV in saliva in human immunodeficiency virus type 1 (HIV-1)-infected patients and mapped specific epitope reactivity of CMV IgG antibodies. Total CMV IgG titers were significantly higher in symptomatic than in asymptomatic HIV-1-infected patients or controls. All CMV-seropositive patients had neutralizing antibodies to CMV. Shedding of CMV in the saliva of AIDS patients occurs despite the presence of serum antibodies with a high capacity to neutralize autologous CMV isolates. The highest IgG reactivity against a CMV envelope protein (gp116), represented by a peptide, was found in patients with advanced HIV disease. In contrast, identical IgG reactivities against a peptide representing the CMV matrix protein were observed in healthy controls and HIV-1-infected persons.

Adult↗
PubMed1994

Improved cell-mediated immune responses in HIV-1-infected asymptomatic individuals after immunization with envelope glycoprotein gp160.

Strong specific T-cell responses to human immunodeficiency virus type 1 (HIV-1) gp160 were induced by immunization with recombinant gp160 (rgp160). It was given as postinfection vaccination to 40 asymptomatic HIV-1 seropositive patients. The participants received 6 doses of 160 micrograms rgp160 administered intramuscularly at 0, 1, 4, 8, 17, and 26 weeks and were monitored for 1 year. Lymphocyte proliferation was performed by cultivating lymphoid cells in vitro with specific antigens and mitogens. After immunization with gp160, specific T-cell proliferative responses were induced in all 40 patients. One week after the sixth immunization at day 180, a substantially increased response was detected in 98% of the patients, with a mean stimulation index value of 195. Furthermore, proliferative responses were also identified, after immunization, against native gp120 and against a peptide representing the V3 region of gp120. In addition to the HIV-specific T-cell responses, increased reactivity to several other non-HIV antigens, including tetanus toxoid, influenza, measles, and cytomegalovirus, were seen after gp160 vaccination. The responses to CMV and measles were interpreted to represent an improved recall antigen response. Such recall antigen responses were few in matched HIV-infected controls immunized with influenza virus only. All patients initially and repeatedly showed a normal capacity of total T-cell activation, evaluated by the mitogen phytohemagglutinin (PHA). The trend in CD4 counts improved in 30 of 40 patients during the year of follow-up. The frequency of increases of proliferative responses to antigens was associated with a better CD4 trend. Addition of zidovudine for 2 weeks after each immunization had no beneficial effects nor did it prevent induction of immune responses. All patients tolerated the immunizations well, and no systemic adverse effects were noted. This is a phase I trial, and no definitive conclusions regarding clinical efficacy can be reached.

Adult↗
PubMed1994

Immunological and virological interactions in patients receiving passive immunotherapy with HIV-1 neutralizing monoclonal antibodies.

Mouse monoclonal antibodies with high human immunodeficiency virus type 1 (HIV-1) neutralizing titers were used for passive immunotherapy of eleven late-state HIV-infected patients. In five patients the serum level of the core protein p24 decreased, while in five cases it remained unchanged. The level of viral RNA in plasma as measured by quantitative polymerase chain reaction (PCR) decreased in four cases, was stable in another four, and increased in three cases. An anti-mouse (HAMA) response developed in eight patients and anti-idiotypic antibodies appeared in six. Immune complexes that formed in patient sera during the treatment were shown to contain mostly envelope glycoprotein gp120 which decreased in nine of the eleven treated patients toward the end of treatment. Antibodies inhibiting gp120 binding to CD4 became detectable or increased in six patients during immunotherapy. Serology of the HIV-1 V3 region was studied for both the HIV-1 IIIB and MN strains with no or very small changes in titer or avidity after treatment. No change in neutralizing titers to strain HTLVIIIB was observed in serum samples collected before and after treatment was terminated. In nine of the eleven patients stimulation of the T lymphocytes to proliferate in vitro when activated by phytohemagglutinin (PHA) was shown to be increased compared to before treatment. Increased T-cell proliferation was also noted with several antigens such as HIV-1 recombinant antigens, cytomegalovirus (CMV), tetanus toxoid (TT), and purified protein derivate of mycobacterium tuberculosis (PPD). These findings indicate a decreased total gp120 content in serum, permitting better T-cell activation.

Adult↗
PubMed1993

Human immunodeficiency virus type 1 and cytomegalovirus in saliva.

The aim of this study was to evaluate whether HIV-1 or cytomegalovirus (CMV) may contribute to oral lesions frequently found in patients with the acquired immunodeficiency syndrome (AIDS). Saliva samples from 63 HIV-1 positive patients and 21 healthy controls were tested for the presence of HIV-1 and CMV using the polymerase chain reaction (PCR) and virus isolation. CMV IgG titres in serum were also compared in the different groups. HIV-1 RNA, but not DNA, was detected in saliva from 15% (9 out of 59) of the HIV-infected patients. There was no correlation between the presence of HIV-1 RNA and oral symptoms in the patients. CMV DNA was detected significantly more frequently in samples from HIV-1 seropositive than from seronegative patients. CMV was detected in saliva from AIDS patients more often than in saliva from patients with mild or no symptoms. CMV IgG titres were also significantly higher in symptomatic than in asymptomatic patients. There was a significant correlation between the presence of CMV DNA and necrotizing gingivitis, and oral Kaposi's sarcoma in the patients, and also between these lesions and the stage of disease. This does not prove that CMV causes these oral lesions, but a direct or indirect role for CMV cannot be excluded.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Fragmin once or twice daily subcutaneously in the treatment of deep venous thrombosis of the leg.

In an open, randomised controlled study, 101 patients with phlebographically diagnosed deep vein thrombosis of the leg, not extending into more than two thirds of the femoral vein, were randomised to receive Fragmin (a low molecular weight heparin) administered subcutaneously either once or twice daily in doses of 200 U(anti-FXa)/kg/24h or 100 U(anti-FXa)/kg/12h respectively. Prior to Fragmin unfractionated heparin had been administered by continuous iv infusion for not longer than 24h. Warfarin was administered from the first treatment day. Fragmin was administered for at least 5 days or until the prothrombin complex had been within the therapeutic range for at least 2 days. Patients were kept in bed for the first day but thereafter were ambulant. Phlebography was repeated at 5-7 days. Comparison of the phlebograms revealed a similar improvement (reduction in Marder score) in both groups. There were 5 cases of bleeding: 1 major and 3 minor in the twice daily group and 1 minor bleed in the once daily group. There were no cases of clinical pulmonary embolism. It is concluded that Fragmin, administered as a single daily subcutaneous injection, is effective in the treatment of deep vein thromboses, and offers the advantages of reduced costs, despite higher price of the drug, including reduced nursing time.

Adult↗
PubMed1991

Hepatic D-galactosamine toxicity studied with localized in vivo 31P magnetic resonance spectroscopy in intact rats.

Spatially resolved 31P magnetic resonance spectroscopy (MRS) at 4.7 T was applied to noninvasively assess liver phosphorus metabolites in a biochemically well-characterized model of hepatotoxicity induced by injection of a sublethal dose of D-galactosamine (galN). A newly developed hybrid method based on spectral localization with B0 and B1 gradients was employed to obtain multivoxel spectra in intact anesthesized rats. Spatially localized in vivo spectra were recorded 0 to 26 h after galN injection of female rats. In response to galN exposure, diphosphodiester peaks ascribed to UDP-hexosamines became detectable by 4 h and persisted up to 26 h. A metabolite coresonating with inorganic phosphate increased rapidly in intensity by 2 h after galN and returned to baseline by 18 h; this resonance was shown not to be Pi and was assigned to galN-1-phosphate by subsequent high resolution MRS experiments on extracts prepared from these livers. These results confirmed in vivo the metabolic perturbations described previously for this model of hepatotoxicity following biochemical studies based on classical extraction methods. Unlike the in vitro studies, however, these noninvasive experiments provided additional information on the time course of metabolic alterations on the same animal.

Adenosine Triphosphate↗
PubMed1991

A prospective study of 115 initially asymptomatic HIV infected gay men in Stockholm, Sweden.

A cohort of 115 asymptomatic gay men, all seropositive for HIV, was recruited in a health screening project in Stockholm, Sweden, between Nov. 1982 and Dec. 1983 and subsequently followed and clinically evaluated after a mean observation time of 63 months. AIDS in accordance with the surveillance definition (CDC group IV C-1 and D) developed in 34 (29.6%) of the men, while 1 (0.9%) additional man died of multiple myeloma classified as CDC group IV E. Constitutional symptoms (CDC group IV A) developed in 13 (11.3%) men, while symptoms from the central nervous system classified as CDC group IV B occurred in 1 (0.9%) additional man. Minor opportunistic infections included in the definition for CDC group IV C-2 developed in 12 (10.4%) men, while 48 (41.7%) men remained asymptomatic, with or without persistent generalized lymphadenopathy (PGL). One man who died of AIDS had been treated for malignant melanoma (MM) and one who did not fulfill the criteria for CDC group IV died of MM during the observation period. The 5-year actuarial progression rate to surveillance defined AIDS was 31.5% and to CDC group IV 53.6%. No statistically significant association was found between disease progression and a number of recorded epidemiological variables, most previous and present sexually transmitted diseases (STD) (except gonorrhoea) and the presence of PGL at entry. On the other hand, reduced delayed cutaneous hypersensitivity, in particular to tuberculin, as well as the presence of a high IgG titer against cytomegalovirus (CMV), were correlated to disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT).

In a prospective, randomized, open study 119 consecutive patients with phlebographically verified deep venous thrombosis (DVT) of the leg (36% distal and 64% proximal) were treated either with a low molecular weight heparin (Fragmin, Kabi-Vitrum) subcutaneously (120 anti-FXa U/kg) twice daily or standard heparin (SH) as continuous intravenous infusion (480 IU kg-1 day-1). The Fragmin doses were adjusted to achieve an anti-FXa activity of 0.2-0.4 U/ml before injection and not greater than 1.5 U/ml 4 h after the morning injection. The SH dose was modified to prolong the APTT 2-3 times. Repeat phlebography after 5-7 days showed improvement in 34/45 patients (76%) in the Fragmin group and in 30/49 patients (61%) in the SH group and progress in 2/45 (4%) and 3/49 (6%), respectively. The mean Marder scores decreased from 18.7 +/- 12.1 to 15.7 +/- 12.7 in the Fragmin group and from 16.9 +/- 12.0 to 14.4 +/- 11.8 in the SH group (ns). Two patients in the SH group and none in the Fragmin group had major bleedings. After 22 +/- 7 months follow up 6 rethromboses had occurred in the SH group and 4 in the Fragmin group. Postthrombotic signs and symptoms were similar in both groups. We conclude that two daily sc Fragmin doses seem as effective and safe as continuous SH in the treatment of DVT of the leg.

Adult↗