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H Kuiper

Publications and source records attributed to H Kuiper.

At least 73 records · Page 4Linked to original sources
PubMed2001

Molecular characterization and chromosome assignment of the porcine gene for leukemia inhibitory factor LIF.

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine involved in early conceptus development in pig. We isolated a PAC clone containing the porcine LIF gene and determined the complete DNA sequence of the gene, which spans about 6.3 kb and consists of five exons including three alternative first exons (1D, 1M, 1T) spliced onto common second and third exons. The LIF-D transcript encodes a protein of 202 amino acids sharing 87, 84, and 78% identity with respectively human, ovine, and murine leukemia inhibitory factors. The LIF-M and LIF-T transcripts both encode a truncated protein of 158 amino acids. Two SNP markers within untranslated regions of the LIF cDNA were identified. One SNP is located in the 5'-UTR of the alternative exon 1T while the other SNP is located in the 3'-UTR of exon 3. Based on fluorescence in situ hybridization and radiation hybrid mapping, the porcine LIF gene was assigned to chromosome 14q2.1-->q2.2.

Alleles↗
PubMed2001

Characterization and comparative mapping of the porcine CTSL gene indicates a novel synteny between HSA9q21-->q22 and SSC10q11-->q12.

Cathepsin L (CTSL) is a lysosomal cysteine protease with potent elastase and collagenase activities. Its high activity in the uterine lumen during the period of placental attachment has led to speculation that CTSL may play an important role during embryonic implantation in the pig. Cathepsins have also been implicated in blastocyst implantation in other species like cat, rat and man. We isolated a PAC clone containing the porcine CTSL gene and determined the complete DNA sequence of the gene, which spans about 5.6 kb and consists of eight exons. The CTSL transcript encodes a primary peptide of 334 amino acids sharing 73-78% identity with other mammalian cathepsin L precursor proteins. Based on fluorescence in situ hybridization and radiation hybrid mapping, the porcine CTSL gene was assigned to chromosome 10q11--> q12.

Amino Acid Sequence↗
PubMed1999

The communicable disease impact of eliminating publicly funded prenatal care for undocumented immigrants.

OBJECTIVES: In 1996, California proposed regulations to eliminate publicly funded prenatal care for undocumented immigrants. Prenatal treatment of sexually transmitted infections (STIs) can prevent STI-related adverse outcomes of pregnancy (AOP). The study assessed the STI-related health and economic impact of the proposed regulations in Los Angeles County (LAC). METHODS: We modeled excess STI-related AOPs and associated costs that would occur in LAC as if the regulations were implemented in 1995. Using attributable fractions in the exposed for five STIs and their associated AOPs, we calculated excess STI-related AOPs and their costs that would result from the regulations and the degree to which excess morbidity would offset gross savings. RESULTS: The model indicates that, depending on regulatory level, 74, 110, or 132 excess AOPs would occur subsequent to the regulations, representing lost prevented morbidity. These excess AOPs would cost $5.1, $7.6, or $9.2 million dollars in direct medical expenses, offsetting anticipated savings by 19.2%, 29.0%, or 34.9%. This analysis does not include other costs of these STIs or costs associated with non-STI-related sequelae of diminished prenatal care, all of which could further offset anticipated savings. CONCLUSIONS: The proposed regulations would likely lead to increased STI-related morbidity and costs, thereby offsetting anticipated savings. Health departments are in a special position to promptly respond to policy issues affecting vulnerable populations. The development of a practical and rational framework for local-level policy assessment can be important for encouraging good scientific approaches that respond to calls for reductions in basic preventive health services.

California↗
PubMed1999

Does ursodeoxycholic acid mediate immunomodulatory and anti-inflammatory effects in patients with primary sclerosing cholangitis?

BACKGROUND AND OBJECTIVES: Therapy with ursodeoxycholic acid (UDCA) has been reported to be associated with improvements in abnormal serum biochemical liver tests in patients with primary sclerosing cholangitis (PSC). To evaluate further the effects of UDCA on this disease, we evaluated immunological markers and indices of inflammation during a one-year, prospective, open-label trial of UDCA therapy in patients with PSC. PATIENTS AND METHODS: Seventeen PSC patients were enrolled for one year of treatment with UDCA 12-15 mg/kg/day. Serum biochemical variables, immunological markers and indices of inflammation were compared before and at the end of therapy and 4 months after treatment had been withdrawn. Liver histology and immunohistochemistry for human leucocyte antigen (HLA) class I/II and intercellular adhesion molecule 1 (ICAM-1) expression were compared before and at the end of therapy. RESULTS: UDCA treatment was associated with significant improvements in serum biochemical liver tests, immunoglobulin levels and blood coagulation factors. Tumour necrosis factor alpha (TNF-alpha) production after in vitro whole-blood phytohaemagglutinin (PHA) stimulation was increased, but unaltered by UDCA therapy. Baseline serum levels of interleukin-6 (IL-6) and soluble IL-2 receptor were normal, and serum IL-8 levels were increased, but none of these variables was significantly affected by UDCA therapy. Liver histological stage/grade and HLA class I/II and ICAM-1 expression on biliary epithelial cells and hepatocytes were not markedly altered by UDCA therapy. CONCLUSIONS: UDCA therapy in PSC patients was associated with a decrease in cholestasis, but no consistent improvement in hepatic inflammation, fibrosis or histological stage of the disease. Immunomodulatory effects of UDCA in PSC do not appear to be HLA-restricted.

Adjuvants, Immunologic↗
PubMed1999

Immunohistochemical analysis of inflammation in primary sclerosing cholangitis.

OBJECTIVES: There are only limited data about the nature of the mononuclear infiltrate surrounding the affected biliary canaliculi in primary sclerosing cholangitis (PSC). The aim of this study was to characterize the composition of the mononuclear infiltrate and to detect signs of activation/ proliferation among the various subpopulations involved. Furthermore the putative role of the biliary epithelium as antigen presenting cells (APC) was assessed. METHODS: Liver biopsies of 14 PSC patients were analysed. Seven liver specimens of non-inflammatory liver disease (NIL) patients with hepatocellular carcinoma or metastasis from colorectal carcinoma, as well as eight liver biopsies of primary biliary cirrhosis (PBC) patients, served as controls. Paraffin embedded material was stained with GB7, anti-CD3, anti-CD20, anti-CD45RO. Deep frozen sections were stained with anti-CD4, anti-CD8, anti-CD25, anti-CD86, anti-HLA-DR, anti-IFNgamma, anti-IL4, anti-ICAM1 and anti-alpha4beta7. Stainings were scored by two pathologists using a semiquantitative scale. RESULTS: The portal infiltrate was found to consist mainly of CD3+CD45RO+ cells. Few cells expressed activation or proliferation markers in any of the liver specimens. In the PSC-material, significantly more of the infiltrative lymphocytes were positive for the integrin alpha4beta7, as compared to hardly any positive cells in the NIL-group (P < 0.001) and < 10% in the PBC-specimens (P < 0.01). Variable HLA-DR expression of the biliary epithelium was observed in all groups, however, without co-expression of ICAM1 or B7.2. CONCLUSIONS: The portal infiltrate in PSC liver histology specimens appears to consist mainly of non-activated memory T-lymphocytes, a substantial proportion of which expresses the gut-homing integrin alpha4beta7. An antigen-presenting role for the biliary epithelium could not be demonstrated.

Adult↗
PubMed1998

Ursodeoxycholic acid therapy for primary sclerosing cholangitis: results of a 2-year randomized controlled trial to evaluate single versus multiple daily doses.

BACKGROUND/AIMS: Ursodeoxycholic acid has been reported to be of potential benefit for primary sclerosing cholangitis but little is known about the long-term biochemical, histological and radiological efficacy or the optimum frequency of ursodeoxycholic acid administration. METHODS: A 2-year multicentre randomised controlled trial was initiated to assess the effects of ursodeoxycholic acid (10 mg kg(-1).d(-1), given in either single or multiple daily doses, on symptoms, serum liver tests, cholangiographic and histological findings and the occurrence of treatment failure. Liver biopsies were taken and endoscopic retrograde cholangiography was performed at entry and after 2 years; follow-up examinations were at 3-month intervals. Treatment failure was defined as death, liver transplantation, 4-fold increase in serum bilirubin, variceal bleeding, de novo ascites or cholangitis. Actuarial survival was compared with predicted survival using the revised Mayo natural history model for primary sclerosing cholangitis. RESULTS: Forty-eight patients were enrolled. In one case, ursodeoxycholic acid had to be discontinued because of gastro-intestinal complaints. No other side-effects were observed. After 2 years of follow-up, treatment was not associated with a beneficial effect on either symptoms or liver histology. Serum liver tests (alkaline phosphatase, y-glutamyl transferase, aspartate aminotransferase) improved significantly in both groups, while serum bilirubin (which was near normal at entry) and IgG remained stable. No major changes in radiographic bile duct appearance seemed to be present. After 2 years, actuarial survival was 91% (95 CI 83%-99%), which is comparable to the predicted 97% survival rate. Treatment failure occurred in 15% of cases. No significant differences in any of the study endpoints (symptoms, serum liver tests, cholangiographic findings, histology, disease progression) were found between the two groups. CONCLUSIONS: Ursodeoxycholic acid is well tolerated in primary sclerosing cholangitis. Significant effects on biochemical parameters were found and symptoms, bilirubin and histology did not deteriorate. No advantage of a multiple daily dose over a single dose was observed.

Adult↗
PubMed1995

Engagement of CD27 with its ligand CD70 provides a second signal for T cell activation.

Molecules of the TNF-R family have been shown to be essential in the regulation of lymphocyte growth and differentiation. The TNF-R family member CD27 binds to a type II transmembrane molecule belonging to the TNF gene family (CD27L) that is identical to the lymphocyte activation Ag CD70. Using transfected mouse fibroblasts expressing human CD70, we demonstrate here that interaction of CD27 with its ligand provides a potent second signal for cytokine production, induction of activation Ags, and proliferation of unprimed CD45RA+, and to a lesser extent, of primed CD45R0+ peripheral blood T cells. In contrast to costimulatory signals delivered via the CD28-ligand B7-1 (CD80), CD70 was found to induce relatively low IL-2, IL-4, and IL-10 but comparable TNF-alpha secretion. Proliferation of CD45RA+, but not of CD45R0+ T cells, was found to be largely resistant to blocking of IL-2/IL-2R interaction. Finally, the finding that CD70 and CD80 cooperate in the induction of T cell proliferation indicates that cooperation of both molecules may be essential for optimal T cell stimulation. The interaction between CD27 and its ligand CD70 might be of particular importance for the recruitment of T cells from the unprimed T cell pool. Moreover, as CD70 expression in vivo is confined to activated B and T lymphocytes, only a limited set of APC are able to generate this specific second signal for T cell expansion.

Antibodies, Monoclonal↗
PubMed1995

Evidence for intact costimulation via CD28 and CD27 molecules in hyporesponsive T cells from human immunodeficiency virus-infected individuals.

In the activation of T cells, the primary signal is antigen-specific and given through T cell receptor (TcR)/CD3 ligation. Furthermore, costimulatory molecules such as CD28 and CD27, provide an essential signal for activation through interaction with their ligands, present on the membrane of antigen-presenting cells. During asymptomatic human immunodeficiency virus (HIV)-1 infection, T cell function is progressively lost. Here, we investigated whether in the presence of impaired responses of T cells from HIV-infected individuals to signal one, costimulation through CD28 and CD27 after interaction with their natural ligands CD80 and CD70 is intact. T cell proliferative responses to signal one in combination with CD80 or CD70 were decreased in a large fraction of asymptomatically HIV-infected individuals. This was due to impaired responses of signal one but not to impaired responses to costimulation, since CD80 or CD70 did enhance signal one-mediated proliferative responses to a normal extent. Moreover, in individuals with proliferative responses to signal one that were decreased to 50% of normal T cell responses, costimulation even was increased compared to controls. Our results demonstrate that in HIV-infected individuals the response to costimulation is relatively preserved compared to responses to the first signal and point to the defect in T cells in HIV infection being primarily in the CD3/TcR-mediated pathway.

Antigens, CD↗
PubMed1994

Lyme borreliosis.

Explore the source record for details and available documents.

Borrelia burgdorferi Group↗
PubMed1994

Differences in responsiveness to CD3 stimulation between naive and memory CD4+ T cells cannot be overcome by CD28 costimulation.

Activation of naive CD4+ T cells is essential for the induction of primary immune responses. However, this subset is less responsive to signaling via T cell receptor/CD3 (TcR/CD3) complex than memory CD4+ cells. For mitogenic activation of T cells, in addition to triggering of the TcR/CD3 complex, costimulatory signals are required that can be generated by surface structures present on the antigen-presenting cells. We investigated here whether differences in responsiveness to TcR/CD3 stimulation of naive and memory cells can be overcome by the costimulatory pathway B7/CD28. Using a B7-dependent system we show that even in the presence of optimal CD28 costimulation, CD4+ naive cells still have more stringent TcR/CD3 activation requirements than memory cells. Furthermore, titration of the B7 signal revealed that for activation of naive CD4+ cells a higher level of cross-linking of CD28 molecules is required than for memory cells. Thus, our results show that at least two signals are required for activation of both CD4+ memory and naive cells, but that for activation of naive cells higher cross-linking of both CD3 and CD28 molecules is necessary.

Animals↗
PubMed1994

Evaluation of central nervous system involvement in Lyme borreliosis patients with a solitary erythema migrans lesion.

To determine whether early dissemination of Borrelia burgdorferi to the central nervous system occurs in stage I of Lyme borreliosis, neurological and cerebrospinal fluid examination was performed in 48 consecutive patients in whom the only sign of infection was a solitary erythema migrans lesion. Long-term follow-up after treatment with tetracycline was carried out by telephone interview. At presentation, neurological findings were normal in all 48 patients. Cerebrospinal fluid samples were obtained from 29 (60%) patients. Mild pleocytosis and mild impairment of the blood-brain barrier were present in four and one of these patients, respectively. No significant amount of tumor necrosis factor or interleukin 6 was found in the cerebrospinal fluid samples. Culture results of 13 cerebrospinal fluid samples were negative. Borrelia burgdorferi DNA was only detected by the polymerase chain reaction in one of two aliquots of the cerebrospinal fluid sample of one patient. None of 46 patients who were interviewed 12 to 51 (median 25) months after antibiotic treatment developed manifestations consistent with disseminated or chronic Lyme borreliosis. Thus, no compelling evidence was found for the presence of asymptomatic central nervous system involvement in patients with clinically localized Lyme borreliosis.

Adult↗
PubMed1994

Establishment of a microbiologically acceptable daily intake of antimicrobial drug residues.

A model is presented to calculate the microbiologically acceptable daily intake (ADIm) of antibiotic residues in food products. The ADIm calculation is based on MIC values for indicator bacteria Escherichia coli, Bacteroides fragilis, Bifidobacterium spp. and Eubacterium spp., established under gut-like conditions in an in vitro simulation model. The maximum residue level (MRL) for residues in food products can be derived from the ADIm. Four phases can be distinguished in this gastro-intestinal simulation model, namely: 1. In vitro determination of the MIC for each bacterial strain by a standard method. 2. Incorporation of the drug into food (meat, milk) followed by testing of the stability of the antibiotic under gut-like conditions. 3. Adjustment of the 'gastric' fluid to the duodenal situation, inoculation with the test bacteria and anaerobic incubation at 37 degrees C for at least 18 h. 4. MIC reading confirmed by counting bacteria growing on specific solidified media. In this study the method for calculation of ADIm and MRL is given for flumequine as model drug. On the basis of MIC50 values for E. coli strains, a MRL for flumequine of 1.0 microgram/g meat or 0.25 microgram/ml milk was calculated. It is suggested that, depending on the antibacterial spectrum of the antibiotic involved, the ADIm can be determined with selected indicator bacteria, incubated under simulated gastrointestinal conditions.

Anti-Bacterial Agents↗
PubMed1994

Solitary erythema migrans: a clinical, laboratory and epidemiological study of 77 Dutch patients.

Regional variations in the clinical spectrum of Lyme borreliosis have been described previously. These may be related to strain variations, or reflect selection bias. We compared the clinical and epidemiological profiles of Dutch patients presenting with solitary erythema migrans alone, with the profiles in other European studies, and studies from the U.S.A., and cultured Borrelia burgdorferi from erythema migrans to identify the genospecies. Seventy-seven consecutive patients with a final diagnosis of erythema migrans were admitted into the study. Various clinical and epidemiological data were obtained, and serum was evaluated for antibodies to Borrelia burgdorferi with an enzyme-linked immunosorbent assay. Skin biopsy specimens were taken from the border of the erythema migrans and cultured in modified Kelly's medium. The different genospecies of Borrelia burgdorferi were identified by reactivity with monoclonal antibodies H3TS, LA-26, LA-31 and D6, and by rRNA gene restriction patterns. Patients were treated with tetracycline or doxycycline, and were seen for follow-up 6 weeks after treatment. Long-term follow-up was by telephone interview. A tick bite had been noticed by 45% of the patients. The onset of erythema migrans occurred in 97% of these patients within 3 months of the tick bite. Erythema migrans was present for 1-319 days (median 2 months). No concomitant manifestations were spontaneously reported. Borrelia burgdorferi was cultured from 52 (84%) of 62 skin biopsy specimens. Fifty isolates (96%) were identified as Borrelia burgdorferi group VS461. No therapy failures occurred among patients treated with tetracycline (follow-up 1-4 years, median 27 months) or doxycycline (follow-up 6-31 months, median 19 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Isolation of Borrelia burgdorferi from biopsy specimens taken from healthy-looking skin of patients with Lyme borreliosis.

Erythematous skin lesions due to infection with Borrelia burgdorferi will often disappear without antibiotic treatment. The aim of the study was to assess whether after disappearance of the erythematous skin lesion B. burgdorferi is still present in the healthy-looking skin of untreated patients. In six patients, a skin biopsy specimen was taken at the site of a previous erythematous skin lesion 1 to 6 months after disappearance of the lesion. Four of them presented with early disseminated Lyme borreliosis. In one additional patient with early disseminated Lyme borreliosis, the site of a previous tick bite was biopsied. None of these patients had been treated with antibiotics before presentation. The cultures of the skin biopsy specimens of the seven patients showed growth of Borrelia species. By rRNA gene restriction analysis and genospecies-specific PCR, six isolates were classified as Borrelia garinii and one as Borrelia group VS461. These results show that B. burgdorferi can still be cultured from the skin after disappearance of the erythematous skin lesion or at the site of a previous tick bite.

Adolescent↗
PubMed1994

Seroconversion for Lyme borreliosis among Dutch military.

Few prospective studies for Lyme borreliosis (LB) have been conducted among subjects at risk to acquire this disease during their work when wearing well-defined protective clothing against tick-bites. We prospectively compared the rate of seroconversion and the occurrence of clinical manifestations of LB among 2 groups of Dutch military. The at risk-group worked predominantly outdoors, and the control-group conducted predominantly indoor activities. During outdoor work, the at risk-group wore long sleeves, long trousers, closed around the ankles and high boots. Initial serum samples from 2158 military were collected immediately after entering the service. From 932 military (at risk-group: 469, control-group: 463) a second sample was drawn 9 to 12 months later. Sera were tested for IgG and IgM antibodies by ELISA. Four persons (0.9%) in the at risk-group and 10 persons (2.2%) in the control-group seroconverted for IgG and/or IgM antibodies against B. burgdorferi. This difference was not statistically significant. Only 1 person who had seroconverted had noticed an erythema migrans. In conclusion, military performing outdoor activities have a low risk for infection with B. burgdorferi, most likely because they wear protective clothing. Among seroconverted persons clinical manifestations of Lyme borreliosis occurred rarely.

Adolescent↗
PubMed1993

Long-term effects of ceftriaxone treatment on intraocular Lyme borreliosis.

Twelve patients with intraocular Lyme borreliosis suffering from vitreitis were treated with ceftriaxone intravenously. Eight patients had definitive Lyme borreliosis, and tentative diagnosis was made in four patients. After treatment with ceftriaxone, all 12 patients were followed up for more than one year. Vitreitis diminished in all patients and visual acuity improved in six patients. The best results were achieved in patients with definitive Lyme borreliosis.

Adult↗