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Biomedical subjects

B Kupfer

Publications and source records attributed to B Kupfer.

At least 19 recordsLinked to original sources
PubMed2006

Structured treatment interruptions following immediate initiation of HAART in eight patients with acute HIV-1 seroconversion.

BACKGROUND: The immunological and clinical benefits of structured treatment interruptions (STIs) during primary HIV-1 infection remain largely unclear. PATIENTS AND METHODS: Eight patients identified during primary HIV-1 infection were immediately treated with HAART and underwent subsequent STIs after reaching complete viral suppression of HIV-RNA in peripheral plasma. HAART was re-initiated if either HIV-1 RNA >5000 copies/ml, CD4-cells <200 cells/microl or symptomatic HIV-1 disease was observed. RESULTS: After treatment discontinuation, four of eight patients were able to persistently control HIV-1 viremia below 5000 copies/ml until the last time point of follow-up (median 3 years). CD4-cell counts were within the interquartile range of untreated individuals compared to historical reference data from the MACS cohort. In the remaining study subjects persistent virological control was not reached despite repeated STIs. Moreover, compared to the MACS cohort repetitive virological failures during STIs appeared to induce an accelerated decline of CD4-cells. CONCLUSION: Spontaneous HIV-1 control after treated primary HIV-1 infection was possible in four out of eight individuals, however, if STIs after treated primary infection ameliorate the overall HIV-1 disease progression remains unknown. In the absence of viral control, repetitive viral exposure during STIs might be associated with accelerated decline of CD4-cell counts.

Acute Disease↗
PubMed2004

HIV evolution: CTL escape mutation and reversion after transmission.

Within-patient HIV evolution reflects the strong selection pressure driving viral escape from cytotoxic T-lymphocyte (CTL) recognition. Whether this intrapatient accumulation of escape mutations translates into HIV evolution at the population level has not been evaluated. We studied over 300 patients drawn from the B- and C-clade epidemics, focusing on human leukocyte antigen (HLA) alleles HLA-B57 and HLA-B5801, which are associated with long-term HIV control and are therefore likely to exert strong selection pressure on the virus. The CTL response dominating acute infection in HLA-B57/5801-positive subjects drove positive selection of an escape mutation that reverted to wild-type after transmission to HLA-B57/5801-negative individuals. A second escape mutation within the epitope, by contrast, was maintained after transmission. These data show that the process of accumulation of escape mutations within HIV is not inevitable. Complex epitope- and residue-specific selection forces, including CTL-mediated positive selection pressure and virus-mediated purifying selection, operate in tandem to shape HIV evolution at the population level.

Adult↗
PubMed2002

[Do polymorphisms of the SDF1 and CCR2b genes modify the course of hepatitis C or HIV/HCV co-infection?].

BACKGROUND AND OBJECTIVE: Complementary to the CCR5-Delta32 mutation polymorphisms in the genes of CCR2b (CCR2b-V64 I) and stromal derived factor (SDF)-1 (SDF-1 3'A) affect the course of the human immunodeficiency virus (HIV) infection. While the CCR5-Delta32 mutation is also increased in chronic hepatitis C virus (HCV) infection it is unclear, whether the CCR2b-V64 I and the SDF-1 3'A polymorphisms also are associated with chronic HCV infection. METHODS: We analyzed the frequencies of the CCR2b-V64I and SDF1 - 3'A mutation in patients with HIV/HCV coinfection (n = 130), HIV infection (n = 105), HCV infection (n = 153) and 112 healthy blood donors. We stratified each group into homozygous mutations, heterozygous mutations and homozygous wild types, respectively. The resulting subsets were compared with respect to HIV and HCV loads, CD4 and CD8 cell counts. RESULTS: The mutant SDF1 - 3'A allele was found at 20.3 % frequency in patients with HCV infection and at 20.4 % frequency in patients with HIV/HCV coinfection, respectively. It was present in 27.1 % of the patients with HIV infection and 27.9 % of the healthy controls (not significant). The number of SDF-1 3) A homozygous patients was highest in patients with HIV/HCV coinfection and significantly different compared to the Hardy-Weinberg equilibrium (p = 0.010, chi (2) = 9.15). However, CD4- and CD8-cell counts or viral loads were not affected by this mutation. The frequency of the CCR2b-V64 I allele was similar in all patient groups. However, CCR2b-V64 I heterozygous patients showed HIV loads that were threefold lower than in CCR2b wildtype patients (22.9 x 103 vs. 6.4 x 103 copies/ml, not significant). Furthermore, hepatitis C viral loads were reduced roughly by 30 %. CONCLUSION: These results suggest that the SDF1 - 3'A and CCR2b-V64I mutations do not affect the course of HCV and HIV/HCV infection in the same manner as does the CCR5-Delta32 mutation.

Adolescent↗
PubMed2001

Case report. Fungaemia due to Penicillium piceum, a member of the Penicillium marneffei complex.

Due to the inability of most Penicillium species to grow at 37 degrees C, systemic non-marneffei infections are very rare in the human host. We describe a case of fungemia due to Penicillium piceum in a female patient, who died a few days after repeated isolation of this fungus from blood cultures. The species is a member of the section Biverticillata of Penicillium, as was confirmed by rDNA Internal Transcribed Spacer (ITS) sequence data, and hence may share virulence factors with P. marneffei.

Fatal Outcome↗
PubMed2000

Endogenous levels of C-C chemokines MIP-1alpha, MIP-1beta, and RANTES do not reflect the disease course in HIV-seropositive individuals.

It has been shown that the beta (C-C) chemokines macrophage inflammatory protein-1alpha/beta (MIP-1alpha/beta) and RANTES, which are released by CD8+ T cells, are potent inhibitors of HIV viral replication in vitro. To investigate whether serum concentrations of these chemokines reflect such a protective effect in vivo, we measured these in peripheral blood of 60 HIV seropositive patients, 10 healthy subjects, and 10 disease controls. Values were compared with the CDC disease stages and immunological surrogate markers of disease progression, such as CD4+ count, beta2-microglobulin and 5'-neopterin serum levels. In addition, HIV RNA was measured in sera. All three chemokines were not significantly different between HIV patients and healthy individuals, nor were differences of chemokine levels between the CDC stages significant. Instead, disease controls exhibited significantly more MIP-1alpha and MIP-1beta than normals or HIV patients. Furthermore, within the HIV-seropositive subjects we did not observe any relationship with the surrogate markers of HIV disease, CD4+ count, CD4+/CD8+ ratio, beta2-microglobulin, and 5'-neopterin (all correlations NS). HIV viral load did not correlate with the measured chemokine concentrations (r < 0.1, NS). In conclusion, endogenous levels of MIP-1alpha, MIP-1beta, and RANTES do not reflect the hypothesized protective effect on disease progression in HIV infection. Thus, despite potential beneficial effects of the investigated chemokines, other factors may equally contribute to HIV replication control in vivo.

Adult↗
PubMed1999

Failure of double protease inhibitor therapy as a salvage therapy for HIV-infected patients resistant to conventional triple therapy.

A therapeutic dilemma arises once HIV-infected patients develop a break-through of HIV-replication under potent antiretroviral therapy. Therefore, we studied whether patients (n = 12) who failed double nucleoside reverse transcriptase (NRTI) plus indinavir or ritonavir triple therapy can be rescued when therapy is switched to double protease inhibitor (PI) treatment (nelfinavir and hard gel saquinavir) and stavudine. With the rescue regimen HIV-RNA levels initially dropped from 148,571 +/- 45,258 copies/ml to 9,310 +/- 6, 965 copies/ml at week 4 (p = 0.0117). However, virus load subsequently increased to almost baseline levels (131,230 +/- 37,743 copies/ml) at week 12. Likewise, CD4-cell counts could only be stabilized initially (baseline 267 +/- 51; week 4 296 +/- 65 cells/microl), but gradually declined thereafter (216 +/- 34 cells/microl week 12). Before therapy was switched, the viral protease gene from 5 analyzed patients showed 3-5 amino acid substitutions. Moreover, 4 of these patients had one amino acid substitution associated with resistance to nelfinavir. Our data suggest that HIV-infected patients resistant to indinavir or ritonavir and double NRTI combination therapy respond to double PI nelfinavir/saquinavir and D4T rescue therapy only initially but have no sustained benefit.

Anti-HIV Agents↗
PubMed1999

Protection against parenteral HIV-1 infection by homozygous deletion in the C-C chemokine receptor 5 gene.

OBJECTIVES: To investigate the role of the CC chemokine receptor 5 (CCR5) for parenteral transmission of HIV-1. DESIGN: The prevalence of the delta32 deletion within the CCR5 gene was determined in a cohort of 207 patients, who had received documented amounts of non-antibody-tested and non-inactivated clotting factor concentrate. METHODS: Chromosomal DNA of haemophiliacs was isolated from whole blood. A portion of the CCR5 gene spanning the delta32 deletion was amplified by PCR. The resulting DNA fragments were analysed by agarose gel electrophoresis. RESULTS: The rate of HIV-1 infection was correlated strongly with increasing amounts of inoculated clotting factor concentrate. None of the HIV-positive patients (n = 129) had the delta32/delta32 genotype, whereas 12 out of 78 HIV-negative haemophiliacs had the homozygous delta32 deletion. CONCLUSIONS: The delta32/delta32 genotype was highly protective against HIV-1 infection, even in patients who had received millions of non-inactivated clotting factor units. As it is likely that in the early 1980s plasma pools were contaminated not only with monocyte-tropic HIV-1 strains, CCR5 appears to be the major mediator of HIV-1 infection. Furthermore, we conclude that there must be other protective mechanisms in multiply exposed non-infected haemophiliacs who have wild-type CCR5.

Base Sequence↗
PubMed1998

In vitro cytopathogenicity of the human immunodeficiency virus (HIV)-1 predicts survival in HIV-infected hemophiliacs independent from CD4 cell count.

In addition to quantification of viral load the graded cytopathogenicity of the human immunodeficiency virus may provide prognostic information for the course of HIV infection. However, the prognostic value of graded cytopathogenicity in addition to the CD4 count has not been evaluated in a large longitudinal study. Therefore a total of 216 HIV-seropositive hemophiliacs have been followed up from 1985 to 1998 (mean follow-up 70.4 +/- SD 26 months, median 72, range: 12 to 120 months). In vitro virulence was determined according to cytopathic effects on freshly isolated PBMC of healthy donors and graded from A (strongest cytopathogenic effect) to D (no cytopathic isolate effect). Survival was analyzed among patients with different virus isolates by Kaplan-Meier statistics (log rank) and factors independently associated with decreased survival were analyzed by Cox hazard regression analysis. - A virus isolate A was found in 22 (10.2%) patients, a virus isolate B was found in 21 (9.3%) patients, a virus isolate C was found in 9 (4.2%) and a virus isolate D was found in 10 (4.2%) patients. Mean survival times were 48 months (95% Confidence Interval (CI) = 36 - 60) in patients with isolate A, 72 months (CI = 36 - 108) with isolate B, 84 months (CI = 48-120) with isolate C, 72 months (60 - 96) with isolate D and 96 months (CI = 96 - 108) in patients with a negative virus culture (p < 0.001). Cox regression analysis indicated significant associations with outcome for young age (p <0.001), positive virus culture (p < 0.0001) and CD4 count (p < 0.0001) as independent predictors of survival. The presence of an isolate A revealed the strongest odds ratio (6.3, 95% CI 2.9-13.2). Our data indicate that the presence of a virus isolate A represents a strong risk factor for mortality in the course of HIV infection. Besides quantification of viral load and CD4 count, the graded cytopathogenicity may provide additional information for early and aggressive antiretroviral treatment, since the mean survival in patients with cytopathogenic virus isolates is reduced significantly.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Reactivation of hepatitis B in a long-term anti-HBs-positive patient with AIDS following lamivudine withdrawal.

BACKGROUND/AIMS: In HIV-infected patients, who have recovered completely from an acute hepatitis B infection and become anti-HBs positive, hepatitis B infection may be reactivated after progression to AIDS. CASE REPORT: We present the case of a homosexual male patient with AIDS who developed clinical and serological reactivation of hepatitis B with detectable HBV-DNA 18 years after complete recovery from acute hepatitis B infection. Prior to reactivation, antiretroviral triple therapy including lamivudine was changed to therapy without lamivudine. After reintroduction of lamivudine in the triple therapy, HBV-DNA became undetectable and the patient lost HBsAg and again developed anti-HBs antibodies. CONCLUSION: The hepatitis B in this patient can be explained best by reactivation of persistent HBV infection, possibly because of transient decline in antibodies against HBs-antigen due to a reduction in CD4+ lymphocyte numbers and B cell dysfunction. This observation points to the clinical relevance of HBV persistence in serum and blood cells of anti-HBs-positive subjects for many years after recovery from acute hepatitis B infection. The possible role of lamivudine withdrawal which immediately preceded HBV breakthrough in our patient is noteworthy. Regular monitoring of markers of HBV infection, including HBV-DNA, in patients with AIDS appears justified after discontinuation of lamivudine.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Sodium selenite and N-acetylcysteine in antiretroviral-naive HIV-1-infected patients: a randomized, controlled pilot study.

BACKGROUND: The aim of this work was to study the effects of combined oral administration of N-acetylcysteine (NAC) and sodium selenite (Se) on plasma glutathione (GSH), lymphocyte subpopulations and viral load in asymptomatic human immunodeficiency virus (HIV)-infected patients. METHODS: We used a prospective, randomized and controlled therapy trial with partial crossover. Twenty-four antiretroviral-naive HIV-infected outpatients at Centers for Disease Control (CDC)'93 stages I and II were randomized to receive the antioxidant combination NAC 600 mg t.i.d. and Se 500 micrograms per day for either 24 weeks (group A, n = 13) or from the end of week 12 (group B, n = 11) until the end of week 24. Thus, group B served as untreated control during the first 12 weeks. RESULTS: There was (a) a trend towards an increase in the percentage of CD4+ lymphocytes after 6 weeks (P = 0.08); (b) an increase in the CD4/CD8 ratio after 6 and 12 weeks (P = 0.02 and P = 0.04 respectively); and (c) a decrease in the absolute CD8/CD38 count and percentage of lymphocytes after 6 weeks (P = 0.002 and P = 0.033 respectively) and 12 weeks (P = 0.033, P = 0.1 respectively) in group A compared with the control period of group B. The effects observed in group A were, however, not paralleled to the same extent by group B after crossing-over to treatment after 12 weeks. In addition, erythrocyte glutathione peroxidase (GSH-Px) activity and GSH, glutathionedisulphide (GSSG) concentrations and the reduced/total GSH ratio were not affected by the treatment. Serum selenium levels increased significantly (P < 0.001) upon treatment. Viral load was not altered. CONCLUSIONS: The changes in lymphocyte subsets after NAC/Se treatment were not comparable to those after standard antiretroviral drug therapy. This, however, does not preclude per se possible benefits of antioxidant supplementation in HIV disease.

Acetylcysteine↗
PubMed1998

Role of HIV-1 phenotype in viral pathogenesis and its relation to viral load and CD4+ T-cell count.

The predictive value of HIV-1 phenotype in peripheral blood mononuclear cell (PBMC) coculture and the relation among viral phenotype, viral load, and CD4+ T-cell count were examined in two studies. In study A, 132 HIV-1-infected individuals were examined retrospectively for the relation between the result of their initial HIV cultivation in PBMC coculture and survival rate 6 years later. In study B, 176 patients were examined since 1994 for markers of HIV disease progression. HIV-1 phenotype was determined by PBMC cocultivation, viral load by NASBA HIV RNA QT System, and CD4+ T-cell count by flow cytometry. In study A, the percentage of survival for patients with initial negative virus culture was significantly higher (95%) than in patients with nonsyncytia-inducing (NSI) isolates (78%) and syncytia-inducing (SI) isolates (21%) (P < 0.05 and P< 0.0001, respectively). When SI phenotype was subdivided into moderately cytopathogenic and highly cytopathogenic, significant differences in the rate of survival between these subgroups could be observed (45% vs. 14%; P < 0.05). In study B, progression from negative virus culture to the isolation of NSI variants was associated with increasing viral load (P < 0.0001) but did not affect CD4+ T-cell count significantly (P> 0.07), whereas the switch from NSI to SI virus was accompanied by significant decline of CD4+ T-cells (P < 0.0001) but no change in viral load (P > 0.21). Thus, isolation and phenotyping of HIV represents an additional striking predictive marker for progression of HIV infection.

CD4 Lymphocyte Count↗
PubMed1994

Physical exercise and psychological health.

For individuals who are just beginning to exercise, the very unfit, the elderly and persons suffering from psychiatric disorders, low intensity activity has important potential psychological benefits. Several studies indicate that mental health can be improved by low- or moderate-intensity activity. In 2 studies it could be demonstrated that aerobic exercise plus counselling was more effective in the treatment of depressive disorders than counselling alone. Cross-sectional community studies clearly reveal that after controlling for potential sociodemographic and health-related confounding variables the risk of depression is significantly higher for physically inactive individuals compared with regular exercisers. No final conclusions can be drawn from longitudinal field studies on the predictive value of physical activity on the degree of depressive symptoms. Several biological and psychological hypotheses have been proposed to explain the association between physical activity and mental health, however, there is still a lack of an integrated theoretical model.

Exercise↗
PubMed1991

Quantitative measurements of capillary transport in human brain tumors by computed tomography.

The rate at which water-soluble chemotherapeutic drugs enter brain tumors can be extremely variable. The ability to measure or predict the rate of drug entry may have an important role in treatment. We have developed a method that uses information from contrast-enhanced computed tomographic scans to measure quantitatively the rate of transcapillary transport of iodinated compounds in brain tumors. In a group of 10 patients with brain tumors, we obtained serial measurements of tissue (Am) and arterial plasma (Cp) iodine concentration from timed computed tomographic scans done over 30 minutes, after intravenous infusion of meglumine iothalamate (Conray-60). These measurements were analyzed with a two-compartment pharmacokinetic model and nonlinear least-squares regression methods to obtain K1, a blood-to-tissue transfer constant; k2, a tissue-to-blood rate constant; and Vp, tissue plasma vascular volume. Images of K1, k2, and Vp were reconstructed after calculating these values for each 0.8 x 0.8 x 5-mm volume element of the original data. Mean whole tumor K1 values varied from 2.0 mu 1 gm-1 min-1 in a thalamic astrocytoma to 33.9 mu 1 gm-1 min-1 in a glioblastoma multiforme. The value of k2 varied from 0.034 to 0.108 min-1, and Vp varied from 2.4 to 7.9 ml 100 gm-1. In tumor-free brain, the K1 of meglumine iothalamate was 2.9 mu 1 gm-1 min-1; k2 was 0.058 min-1; and Vp was 2.1 ml 100 gm-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Comparison of transferrin receptors, iron content and isoferritin profile in normal and malignant human breast cell lines.

We studied the mode of iron transport and storage in a human breast cancer cell line (HT-24) in comparison with a breast epithelial cell line (HBL-100). It was found that HT-24 cells incorporated over 18 h more 59Fe as compared to HBL-100 (24 vs. 16%). Yet, the number of surface transferrin-binding sites was less in cancer cells (6.2 x 10(5)) than in epithelial cells (8 x 10(5)). Moreover, the transferrin receptors in cancer cells were less affected by iron overloading as compared with epithelial cells. Following immunoprecipitation of isoferritins with specific monoclonal antibodies (MoAbs), it was found that the quantity of de novo synthesized normal ferritin immunoprecipitated with CM-G-8 MoAb was similar in both cancer and epithelial cells. However, the amount of 59Fe incorporated into the protein was significantly higher in HBL-100 cells. In contrast, HT-24 cells synthesized a high amount of placental-like isoferritin (PLF) immunoprecipitated with CM-H-9 MoAb which was significantly higher (p less than 0.001) than in epithelial cells. This isoferritin was characterized by its low iron incorporation. It is noteworthy that the ratio of PLF to normal ferritin was 2:1 in cancer cells and 0.7:1 in epithelial cells, indicating that PLF is a major type of isoferritin synthesized by HT-24 breast cancer cells. Furthermore, a significant amount of PLF was expressed on the surface of cancer cells as compared to epithelial cells. The results of this study suggest that iron supply and distribution in breast neoplastic cells are not controlled similarly to normal cells.

Adenocarcinoma↗
PubMed1989

Expression of messenger RNA species coding for a Mr 43,000 peptide associated with ferritin in human leukemia-K562 cells and its down regulation during differentiation.

In the current study it was found that K-562 erythroleukemia cells express the superheavy (S) mRNA and the 43 Kd S peptide which were recently discovered in activated T-lymphocytes. The S mRNA was identified by its cross-hybridization with ferritin H complementary DNA probe and the S peptide (Mr 43,000) was identified by its immunoprecipitation with CM-H-9 monoclonal antibody specific for placental isoferritin. During terminal differentiation by hemin the level of S mRNA decreased below detection, with a concomitant diminution in the biosynthesis of the S peptide. In contrast, a significant increase in the level of ferritin light (L) and heavy (H) mRNAs was observed, resulting in an increase in the rate of biosynthesis of the H and L ferritin subunits. Removal of iron by desferrioxamine reduced the biosynthesis of ferritin L and H chains without altering the level of the corresponding mRNAs. Treatment with desferrioxamine did not affect either the level of S mRNA or the biosynthesis of the S peptide. This is a demonstration of a new mRNA species which is expressed in leukemic cells and is down-regulated during cell differentiation.

Cell Line↗
PubMed1989

T-cell mitogenesis stimulates the synthesis of a mRNA species coding for a 43-kDa peptide reactive with CM-H-9, a monoclonal antibody specific for placental isoferritin.

In studying the changes that occur in concanavalin A-activated T lymphocytes, an mRNA species was discovered by hybridization of poly(A)+ mRNA with a human ferritin heavy chain cDNA probe. This ferritin mRNA, termed superheavy chain mRNA, differed from the known human ferritin heavy chain mRNAs by its larger size and degree of homology. The superheavy chain mRNA was isolated by sucrose-gradient centrifugation and translated in vitro in a cell-free system. The products obtained included two peptides (superheavy) of 43kDa that reacted with CM-H-9, a monoclonal antibody specific for placental isoferritin. De novo synthesis in intact transformed T cells revealed the synthesis of the superheavy chain peptides that were immunoprecipitated by anti-ferritin monoclonal antibody CM-G-8 and by placental isoferritin specific monoclonal antibody CM-H-9. The above results indicated that blast transformation of human T cells stimulated the appearance of a unique mRNA species that coded for a superheavy chain peptide associated with placental isoferritin, which was not detected in resting T cells.

Antibodies, Monoclonal↗