PubMed Health⌕ Search

Biomedical subjects

H Jessen

Publications and source records attributed to H Jessen.

At least 19 recordsLinked to original sources
PubMed2005

Treatment of acute hepatitis C infection in HIV-infected patients: a retrospective analysis of eleven cases.

Studies on hepatitis C virus (HCV) monoinfected patients suggest high sustained treatment response rates of up to 98% when interferon monotherapy is administered during the acute phase of HCV-infection. To clarify whether early treatment of acute hepatitis C is similarly efficient in human immunodeficiency virus (HIV) positive patients, we conducted a retrospective survey of HIV-positive patients with acute HCV infection. Eleven HIV-positive patients who had been treated with interferon or interferon/ribavirin were identified at eight HIV-specialty outpatient clinics. The patients had been treated over a median 25 weeks with standard interferon (two patients), pegylated interferon (four patients) and pegylated interferon in combination with ribavirin (five patients). A post-treatment response (negative serum HCV-RNA at the end of treatment) was seen in 10 of 11 patients and HCV-RNA remained undetectable 24 weeks after the end of treatment in all the 10 responders. Alanine aminotransferase (ALT) normalized in eight patients while two virological responders and one nonresponder showed persistent mild ALT elevations. In conclusion, early treatment of acute hepatitis C seems to achieve high sustained virological treatment response rates also in patients with HIV-infection.

AIDS-Related Opportunistic Infections↗
PubMed2002

Predictors of treatment failure during highly active antiretroviral therapy (racing trial).

PURPOSE: To determine factors associated with virological failure during long-term treatment with the triple combination of saquinavir soft gel capsule, zalcitabine and zidovudine. METHOD: Open-label, prospective, multicentre study undertaken in private practices and the outpatient department of the Auguste-Viktoria-Hospital. A total of 95 patients with plasma HIV RNA > 5000 copies/ml who had received no more than 6 months pre-treatment with NRTIs and no prior PI therapy received saquinavir soft gel, zalcitabine and zidovudine for 52 weeks, before being randomly assigned to either remain on therapy or switch to nelfinavir, lamivudine and zidovudine for further 52 weeks. RESULTS: Combination therapy with saquinavir, zalcitabine and zidovudine was found to be effective and well tolerated, with virological response to therapy maintained for up to 2 years. In patients responding to therapy, switching to a novel triple regimen did not result in a virological or immunological worsening, but it did not confer an additional clinical benefit. Factors predictive of early treatment failure (virological failure within 16 weeks of treatment initiation) included high viral load and presence of RT mutations at baseline (OR: 0.30, 95% CI 0.11 0.83 and OR 0.13, 95% CI 0.03 0.52, respectively), with baseline viral load and the development of genotypic mutations on therapy being predictive of late treatment failure (16 52 weeks; OR: 0.15, 95% 0.05 0.46 and OR: 0.26, 95% CI < 0.001 1.16, respectively). Plasma saquinavir concentration < 50 mg/ml at 4 weeks was also found to be an independent risk factor for both early and late treatment failure (OR: 1.80, 95% CI 1.23 2.64 and OR: 1.16, 95% CI 0.84 1.60, respectively). CONCLUSIONS: While antiretroviral drug resistance appears to be a principal cause of treatment failure, other factors such as inadequate drug plasma concentrations also play a role.

Adult↗
PubMed1999

Expansion of CD57 and CD62L-CD45RA+ CD8 T lymphocytes correlates with reduced viral plasma RNA after primary HIV infection.

OBJECTIVE: CD8 T cells, expressing cell surface molecules distinct from those on resting and naive T cells, are increased in HIV infection. The association of increased CD38 and human leukocyte antigen DR (HLA-DR) CD8 T cells with poor prognosis has suggested that activated CD8 T cells may aggravate HIV infection. We examined whether other immunological parameters might influence the viral setpoint. DESIGN: Peripheral T cells from nine untreated patients, obtained after primary HIV infection when plasma HIV had stabilized, were examined for proteins expressed in activated versus resting, memory versus naive, and cytolytic versus non-cytolytic T cells. METHODS: The proportion of CD8 T cells that stain for CD38 and HLA-DR, CD28 and CD57 was compared with plasma viraemia and CD4 cell count. These parameters were also compared with the proportion of CD4 and CD8 T cells that express CD62L and CD45RA, present on naive cells and down-modulated in memory cells. Internal staining for the cytotoxic protein granzyme A was also examined. RESULTS: An increase in CD38 and CD38 HLA-DR CD8 T cells correlated with increased plasma viral RNA (P < 0.00002, P < 0.03, respectively). An increase in CD8 T cells expressing granzyme A was associated with lower CD4 cell counts (P < 0.04). However, the expansion of CD57 and CD62L CD45RA+ CD8 T cells was associated with a lower viral setpoint (P < 0.01, P < 0.02, respectively). CONCLUSION: Phenotypically defined activated CD8 T cells may have different functions in HIV infection. Activated CD8 T cells that are CD57 or CD62L(-)CD45RA+ may be beneficial, because their expansion in untreated patients correlates with a reduced viral setpoint after primary infection.

Adolescent↗
PubMed1999

Immune restoration by combination of a cytostatic drug (hydroxyurea) and anti-HIV drugs (didanosine and indinavir).

Cell activation is essential for HIV infection. CD4+ T lymphocyte activation allows virus replication and CD8+ T lymphocyte activation may contribute to pathogenesis. We combined hydroxyurea, a cytostatic drug that inhibits cell activation and proliferation, with two drugs that inhibit HIV (didanosine and indinavir), to block the "cell activation-virus production-pathogenesis" cycle. HIV was strongly suppressed in treated patients, and the average CD4 count increased to 224/mm3. Compared with a matched group of patients who had declined antiretroviral treatment, treated patients had a significantly lower proportion of activated CD8+ T lymphocytes and a significantly higher number of naive CD8+ and CD4+ T lymphocytes. The proliferative responses to allogeneic and influenza virus antigens were increased in treated patients, and a defect in CD3-zeta expression, the signaling chain of the T cell receptor complex, was reversed. The use of a cytostatic drug was not detrimental to the immune system; on the contrary, the combination of antiviral and cytostatic treatment improved all of the immune parameters tested.

Anti-HIV Agents↗
PubMed1999

Treatment of human immunodeficiency virus infection with hydroxyurea, didanosine, and a protease inhibitor before seroconversion is associated with normalized immune parameters and limited viral reservoir.

Current treatments for human immunodeficiency virus (HIV) require uninterrupted drug administration because they are unable to reconstitute the immune response and do not affect the viral reservoir. Ten patients were treated during acute HIV infection before complete Western blot (WB) seroconversion with the combination of hydroxyurea, didanosine, and indinavir. This treatment was associated with the normalization of some immune parameters and functions. No loss of naive CD4 T lymphocytes was observed, and recovery of up to 35% of naive CD8 T lymphocytes occurred in several weeks. A vigorous HIV-specific T helper response (stimulation index >8) was observed in 7 of 8 patients treated before complete WB seroconversion but in only 1 of 5 controls treated after seroconversion. In addition, a limited latent viral reservoir (<0.02-0.5 infectious units/106 cells) was documented in quiescent peripheral blood lymphocytes after treatment initiated before complete WB seroconversion.

Anti-HIV Agents↗
PubMed1997

Combination of a drug targeting the cell with a drug targeting the virus controls human immunodeficiency virus type 1 resistance.

Combinations of drugs targeting viral proteins have been used to limit or control drug resistance, which is the most important cause of treatment failure in HIV-1-infected individuals. We suggest an alternative approach, namely to target cellular proteins, which are less prone to mutations than viral proteins. Here we show that simultaneous inhibition of a cellular protein (by hydroxyurea) and a viral protein (by ddI) produces a consistent and sustained suppression of HIV-1 for as long as 40 weeks in the absence of virus rebound. We identified the mechanism to explain this lack of rebound: although the combination of the two drugs did not prevent the emergence of mutant viral strains resistant to didanosine (ddI) in these patients, the mutants were still sensitive to standard doses of ddI in the presence of hydroxyurea. These in vivo results were consistent with our in vitro observations: HIV-1 molecular clones resistant to ddI were rendered sensitive to this drug (at concentrations routinely achievable in vivo) after addition of hydroxyurea. This phenomenon can be explained by the observation that hydroxyurea decreases the level of dATP, the cellular competitor of ddI. A low level of dATP favors the incorporation of ddI, even if the viral reverse transcriptase is resistant to this nucleoside analog. This is a novel mechanism of control of resistance and it explains the efficacy of a treatment that is well tolerated, simple, and inexpensive.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Adaptive regulation of taurine and beta-alanine uptake in a human kidney cell line from the proximal tubule.

1. The underlying mechanisms involved in the adaptive regulation of beta-amino acid uptake in the human proximal tubule were examined by use of an immortalized human embryonic kidney epithelial cell line (IHKE). 2. The results indicated that the adaptive response to maintain whole-body taurine homeostasis occurs predominantly via changes in the activity of the high-affinity taurine transport system by alterations in the uptake capacity and with an unaffected half-saturation constant. An adaptive response was not observed for the structurally related beta-alanine. 3. Only colchicine, which interferes with microtubule organization, was capable of blocking the response to alterations of taurine in cell medium, whereas inhibition of protein and nucleic acid synthesis by cycloheximide and actinomycin D, respectively, did not change the adaptive pattern. 4. Phorbol 12-myristate 13-acetate (PMA), mimicking the effects of diacylglycerol, induced inhibition of both beta-alanine and taurine uptake. By contrast, the Ca2(+)-ionophore A23187, mimicking the effects of IP3, only stimulated the uptake of taurine but not the influx of beta-alanine. However, the effect of PMA down-regulation and A23187 up-regulation was rapid and short-lived in contrast to the adaptive response, suggesting that the inositol phospholipid pathway involving diacetylglycerol and IP3 is less likely to be linked directly to the adaptive regulation, but rather plays a role in short-term regulation.

Adaptation, Physiological↗
PubMed1996

Uptake of neutral alpha- and beta-amino acids by human proximal tubular cells.

The transport characteristics of amino acids in primary cell cultures from the proximal tubule of human adults (AHKE cells) were examined, using alpha-aminoisobutyric acid (AIB) and beta-alanine as representatives of alpha- and beta-amino acids, respectively. The Na(+)-gradient dependent influx of AIB occurred by a single, saturable transport system, whereas the Na(+)-gradient dependent uptake data for beta-alanine could be described in terms of two-independent transport components as well as one-transport one-leak model with identical kinetic constants for the high-affinity system. Competition experiments revealed that all the neutral amino acids tested reduced the uptake of AIB, whereas there was no effect of taurine, L-aspartic acid, and L-arginine. By contrast, the influx of beta-alanine was only drastically reduced by beta-amino acids, whereas the inhibition by neutral alpha-amino acids was relatively low. Nor did L-arginine and L-aspartic acid affect the uptake of beta-alanine into AHKE cells. Comparison with the results obtained for normal (NHKE) and immortalized (IHKE) embryonic cells suggested an unaltered expression of the types of transport carriers for neutral alpha- and beta-amino acids in the embryonic and AHKE cells. However, the uptake capacity of the above-mentioned transport proteins was relatively smaller in the embryonic kidney compared with the adult human kidney, which may explain, at least partly, the phenomenon of physiologic amino aciduria in neonates.

Adult↗
PubMed1995

IGF-II receptors in luminal and basolateral membranes isolated from pars convoluta and pars recta of rabbit proximal tubule.

The binding of 125I-labeled insulin-like growth factor-II (125I-IGF-II) to luminal and basolateral membrane vesicles isolated from pars convoluta and the straight part (pars recta) of rabbit proximal tubule was investigated. Analyses of the binding data by use of the general stoichiometric binding equation revealed, that in all preparations IGF-II was bound to one high-affinity binding site and other sites with lower affinities. The specificity of the high-affinity 125I-IGF-II binding to the membrane vesicles assessed by displacement by unlabeled IGF-II, IGF-I and insulin showed that IGF-I displaced 125I-IGF-II in the range 22.5-47.9 nM (IC50) whereas insulin did not effect 125I-IGF-II binding at all. beta-Galactosidase inhibited the 125I-IGF-II binding with half-maximal inhibition of 20-30 nM beta-galactosidase. D-Mannose 6-phosphate increased the binding of 125I-IGF-II and reversed the inhibitory effect of beta-galactosidase. Analyses of 125I-IGF-II binding curves in the presence of beta-galactosidase or D-mannose 6-phosphate demonstrated that none of these compounds changed the binding affinity of 125I-IGF-II for the membrane vesicles. The IGF-II/M6P receptor content in the luminal membranes was in the range 0.21-0.34 pmol IGF-II/M6P receptor per mg protein and very low compared to 2.27-2.86 pmol IGF-II/M6P receptor per mg protein in basolateral membranes.

Animals↗
PubMed1994

Taurine and beta-alanine transport in an established human kidney cell line derived from the proximal tubule.

The transport mechanisms of taurine and beta-alanine by an immortalized human embryonic kidney epithelial cell line (IHKE) were examined. The uptake of these beta-amino acids was characterized by two Na(+)-dependent transport components, whereas an inwardly directed H(+)-gradient only stimulated amino acid influx to a small extent and in the absence of sodium. Competition experiments revealed that taurine and beta-alanine drastically reduced the uptake of one another by the high-affinity Na(+)-dependent transport system. However, some alpha-amino acids could also compete with the beta-amino acids, but with a low affinity. Examinations of the effect of different anions on the Na(+)-dependent uptake of taurine at a low amino acid concentration (240 nM) revealed a specific requirement for Cl-, whereas Cl- had no measurable effect at a higher concentration (1.0 mM) of taurine. In addition, activation of taurine transport as a function of Na+ and Cl- concentration indicated a probable coupling ratio of 3 Na+/1 Cl-/1 taurine for the high-affinity carrier. Finally, cellular regulation of taurine transport was indicated by the finding that pretreatment with taurine containing media decreased the activity of the taurine transporter(s).

Anions↗
PubMed1994

A comparative study on the uptake of alpha-aminoisobutyric acid by normal and immortalized human embryonic kidney cells from proximal tubule.

We investigated whether an immortalized human kidney epithelial cell line (IHKE), compared with normal embryonic cells (NHKE), can be used as a representative system with which to characterize the transport of neutral amino acids in the proximal tubule of the human kidney. The IHKE cell line, immortalized by treatment with NiSO4, exhibited microvilli and enzyme markers specific for highly specialized tubule cells. The Na(+)-dependent uptake of alpha-aminoisobutyric acid (AIB) by IHKE and NHKE cells occurred by means of a single transport system with identical half-saturation constants, but the capacity for uptake was higher in the immortalized cells. Proton-dependent influx of AIB was also mediated by a single transport component with similar uptake characteristics in both types of cells. Imposition of an H(+)-gradient to a Na(+)-gradient reduced the sodium dependent uptake of AIB with the exception of short incubation time (1 min), where addition of a proton gradient produced a marked increase in the Na(+)-dependent influx of AIB in NHKE but not in IHKE cells. Competition experiments revealed that the Na(+)-dependent uptake at 50 microM AIB was reduced by neutral alpha-amino acids in the two cell lines. L-Glutamate, L-aspartate, L-arginine and the beta-amino acid taurine had no effect. Only in the IHKE cell line did addition of 5 mM L-lysine produce a slight inhibition. Except for L-proline all of the neutral and acidic amino acids tested reduced the H(+)-dependent uptake of AIB in the IHKE cell line. By contrast, addition of L-aspartate did not influence the transport of AIB in NHKE cells. L-Arginine, but not L-lysine decreased the influx in both cell lines. We conclude that the IHKE cell line has retained the capability to accumulate AIB by transport protein(s) similar to those present for neutral alpha-amino acids in NHKE cells.

Aminoisobutyric Acids↗
PubMed1992

L-tryptophan uptake by segment-specific membrane vesicles from the proximal tubule of rabbit kidney.

1. The mechanism of the renal transport of L-tryptophan by basolateral and luminal membrane vesicles prepared from either the pars convoluta or the pars recta of the rabbit proximal tubule was studied. The uptake of L-tryptophan by basolateral membrane vesicles from the pars convoluta was found to be an Na(+)-dependent transport event. The Na(+)-conditional influx of the amino acid was stimulated in the presence of an inwardly directed H+ gradient. Lowering the pH without an H+ gradient had no effect, indicating that L-tryptophan is co-transported with H+. 3. On the other hand, no transient accumulation of L-tryptophan was observed in the presence or absence of Na+ in basolateral membrane vesicles from the pars recta. 4. In luminal membrane vesicles from the pars recta, the transient Na(+)-dependent accumulation of L-tryptophan occurred via a dual transport system. In addition, an inwardly directed H+ gradient could drive the uphill transport of L-tryptophan into these vesicles in both the presence and the absence of an Na+ gradient. 5. By contrast, the uptake of L-tryptophan by luminal membrane vesicles from the pars convoluta was a strictly Na(+)-dependent and electrogenic transport process, mediated by a single transport component. 6. Investigation of the coupling ratio in luminal membrane vesicles suggested that 1 Na+:1 L-tryptophan are co-transported in the pars convoluta. In the pars recta, examination of the stoichiometry indicated that approx. 1 H+ and 2 Na+ (high affinity) or 1 Na+ (low affinity) are involved in the uptake of L-tryptophan.

Animals↗
PubMed1991

Stoichiometric studies of beta-alanine transporters in rabbit proximal tubule.

The coupling ratio for the transport of beta-alanine and Na+, H+ and Cl- in luminal membrane vesicles isolated from proximal convoluted tubules (pars convoluta) and proximal straight tubules (pars recta) of rabbit kidney was examined. Indirect evidence indicates that 1 H+ and approx. 2 Na+, 1 Cl- (Na(+)-dependent, high-affinity) or 1 Na+ (Na(+)-dependent, low-affinity) are co-transported with beta-alanine in the pars convoluta. In pars recta, the two Na(+)-dependent transporters exhibited the same stoichiometric properties respectively as in pars convoluta.

Animals↗
PubMed1991

Renal transport of taurine in luminal membrane vesicles from rabbit proximal tubule.

The uptake of taurine by luminal membrane vesicles from pars convoluta and pars recta of rabbit proximal tubule was examined. In pars convoluta, the transport of taurine was characterized by two Na(+)-dependent (Km1 = 0.086 mM, Km2 = 5.41 mM) systems, and one Na(+)-independent (Km = 2.87 mM) system, which in the presence of an inwardly directed H(+)-gradient was able to drive the transport of taurine into these vesicles. By contrast, in luminal membrane vesicles from pars recta, the transport of taurine occurred via a dual transport system (Km1 = 0.012 mM, Km2 = 5.62 mM), which was strictly dependent on Na+. At acidic pH with or without a H(+)-gradient, the Na(+)-dependent flux of taurine was drastically reduced. In both kind of vesicles, competition experiments only showed inhibition of the Na(+)-dependent high-affinity taurine transporter in the presence of beta-alanine, whereas there was no significant inhibition with alpha-amino acids, indicating a beta-amino acid specific transport system. Addition of beta-alanine, L-alanine, L-proline and glycine, but not L-serine reduced the H(+)-dependent uptake of taurine to approx. 50%. Moreover, only the Na(+)-dependent high-affinity transport systems in both segments specifically required Cl-. Investigation of the stoichiometry indicated 1.8 Na+: 1 Cl-: 1 taurine (high affinity), 1 Na+: 1 taurine (low affinity) and 1 H+: 1 taurine in pars convoluta. In pars recta, the data showed 1.8 Na+: 1 Cl-: 1 taurine (high affinity) and 1 Na+: 1 taurine (low affinity).

Amino Acids↗