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Biomedical subjects

M Prins

Publications and source records attributed to M Prins.

At least 55 records · Page 3Linked to original sources

Immunoglobulin A, G, and M responses to L1 and L2 capsids of human papillomavirus types 6, 11, 16, 18, and 33 L1 after newly acquired infection.

OBJECTIVES: We performed a study to establish the pattern of serological reactivity for immunoglobulins (Ig), to capsids of human papilloma virus (HPV) after new HPV infection in two groups of subjects. METHODS: The pattern of serological reactivity after acquisition of infection with HPV was investigated by measuring IgA, IgM, and IgG antibodies to capsids containing L1 and L2 proteins of HPV types 6, 11, 16, 18, and 33 in longitudinal studies of groups with different patterns of sexual activity. Individuals who tested negative for HPV DNA by the polymerase chain reaction at enrolment, but who became HPV DNA positive during follow up, were examined for antibodies to HPV capsids by enzyme linked immunosorbent assay. One group consisted of 15 young girls (with eight controls who remained HPV DNA negative) who were becoming sexually active and the other comprised 12 male (with five controls) and 35 female (with seven controls) heterosexual attenders of a sexually transmitted disease clinic who had had multiple sexual partners. RESULTS: The sexually inexperienced girls showed IgA and IgG responses, but seldom an IgM response to infection with HPV types 6/11, 16, and 18. No consistent pattern of serological reactivity was apparent for the heterosexuals with multiple partners. The lack of association between current HPV DNA positivity and detectable antibodies in these individuals was possibly related to the duration of infection or to prior exposure to HPV. For the latter group serological reactivity to HPV capsids was significantly greater in women than in men (p = 0.001, p = 0.003, and p = 0.024, for IgG to HPV 6, 11, and 16, respectively). CONCLUSION: The sex difference in antibody response detected in previous studies with assays based on peptide antigens was thus corroborated in the present study with capsid based serological assays. This sex difference might reflect a difference in sexual activity and prior exposure to HPV between men and women in this particular group.

Adult↗

Thromboprophylaxis in non-surgical patients: who, when and how?

Because of the serious lack of useable, relevant information, most recommendations for prevention of thrombosis in non-surgical patients are extrapolations from much larger clinical trials experienced in surgery. Directly relevant evidence comes predominantly from very small randomized trials, many of them open label and carried out more than 20 years before the introduction of more recent and important changes in clinical care that may have substantially reduced the baseline thrombosis risk. In these early studies, low-dose heparin and low-molecular-weight heparins prevented subclinical deep vein thrombosis in ischaemic stroke, myocardial infarction and among elderly medical inpatients. Although it is likely that these drugs also prevent subclinical deep vein thrombosis after spinal cord injury or other major trauma, and when patients require intensive medical care, the supporting evidence in these circumstances comes mainly from cohort studies and poorly controlled comparisons. In contrast, the heparins have not reduced mortality or demonstrably prevented pulmonary embolism after ischaemic stroke or among elderly medical inpatients in large and well-conducted clinical endpoint trials, from which no clinically important benefit could be demonstrated. From analyses it is suggested that such benefit is probably more difficult to demonstrate for medical than for surgical patients. In the absence of sufficient information that is specific to medical patients, various forms of prophylaxis known to be effective in surgery will continue to be applied in high-risk individuals. After venous thromboembolism, it now appears that the best duration of oral anticoagulant therapy to prevent a recurrence is determined to a greater extent by whether the thrombotic episode was idiopathic or triggered by a clinically recognizable cause, whether it was transient or continuing, and whether the deep vein thrombosis was extensive, limited to the calf veins or was a first or recurrent event.

Aged↗

Increase in extracellular glutamate caused by reduced cerebral perfusion pressure and seizures after human traumatic brain injury: a microdialysis study.

OBJECT: To determine the extent and duration of change in extracellular glutamate levels after human traumatic brain injury (TBI), 17 severely brain injured adults underwent implantation of a cerebral microdialysis probe and systematic sampling was conducted for 1 to 9 days postinjury. METHODS: A total of 772 hourly microdialysis samples were obtained in 17 patients (median Glasgow Coma Scale score 5+/-2.5, mean age 39.4+/-20.4 years). The mean (+/-standard deviation) glutamate levels in the dialysate were evaluated for 9 days, during which the mean peak concentration reached 25.4+/-13.7 microM on postinjury Day 3. In each patient transient elevations in glutamate were seen each day. However, these elevations were most commonly seen on Day 3. In all patients there was a mean of 4.5+/-2.5 transient elevations in glutamate lasting a mean duration of 4.4+/-4.9 hours. These increases were seen in conjunction with seizure activity. However, in many seizure-free patients the increase in extracellular glutamate occurred when cerebral perfusion pressure was less than 70 mm Hg (p < 0.001). Given the potential injury-induced uncoupling of cerebral blood flow and metabolism after TBI, these increases in extracellular glutamate may reflect a degree of enhanced cellular crisis, which in severe head injury in humans appears to last up to 9 days. CONCLUSIONS: Extracellular neurochemical measurements of excitatory amino acids may provide a marker for secondary insults that can compound human TBI.

Adult↗

Pre-AIDS mortality from natural causes associated with HIV disease progression: evidence from the European Seroconverter Study among injecting drug users.

OBJECTIVES: To study differences in pre-AIDS mortality between European cohorts of injecting drug users (IDU) and to evaluate whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count. METHODS: The study population consisted of 664 IDU with documented intervals of HIV seroconversion from eight cohort studies. Differences in pre-AIDS mortality were studied between European sites; an evaluation of whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count was carried out using Poisson regression. RESULTS: One hundred and seven IDU died, of whom 57 did not have AIDS. Pre-AIDS causes of death were overdose/suicide (49%), natural causes such as bacterial infections/cirrhosis (40%), and unintentional injuries/unknown (11%). Considering pre-AIDS death and AIDS as competing risks, 14.7% were expected to have died without AIDS and 17.3% to have developed AIDS at 7 years from seroconversion. No statistically significant differences in pre-AIDS mortality were found between European regions, men and women, age categories and calendar time periods. Overall pre-AIDS mortality did not increase with time since seroconversion, but did increase with decreasing CD4 count. Evaluating cause-specific mortality, only pre-AIDS mortality from natural causes appeared to be associated with time since seroconversion as well as immunosuppression. For natural causes, the death rate per 100 person-years was 0.13 the first 2 years after seroconversion, 0.73 in years 2-4 [risk relative (RR) to years 0-2, 5.6], 1.83 in years 4-6 (RR, 14.0) and 1.54 for > or = 6 years (RR, 11.7). This rate was 0 for a CD4 cell count > or = 500 x 10(6)/l, 1.06 for 200-500 x 10(6)/l and 4.06 for < 200 x 10(6)/l (RR versus > or = 200 x 10(6)/l, 7.0). In multivariate analysis, both CD4 count and time since seroconversion appeared to be independently associated with death from natural causes; CD4 count appeared to be the strongest predictor (adjusted RR, 5.9). CONCLUSIONS: A high pre-AIDS mortality rate was observed among IDU. No significant differences were observed across European sites. Pre-AIDS mortality from natural causes but not from overdose and suicide was associated with HIV disease progression.

Acquired Immunodeficiency Syndrome↗

Association between CCR5 genotype and the clinical course of HIV-1 infection.

BACKGROUND: Heterozygosity for a 32-nucleotide deletion in the C-C chemokine receptor 5 gene (CCR5 delta 32) is associated with delayed disease progression in persons infected with HIV-1. OBJECTIVE: To compare the predictive value of CCR5 genotype with that of established markers in the clinical course of HIV-1 infection. DESIGN: Retrospective longitudinal study and nested case-control study. The latter included only long-term survivors, who were individually matched with progressors. SETTING: Amsterdam, the Netherlands. PARTICIPANTS: 364 homosexual men with HIV-1 infection. MEASUREMENTS: Polymerase chain reaction was used for CCR5 genotyping. Univariate and multivariate Cox proportional hazard analyses were done for disease progression with CCR5 genotype, CD4+ T-lymphocyte counts, T-lymphocyte function, HIV-1 biological phenotype (syncytium-inducing or non-syncytium-inducing HIV-1), and viral RNA load in serum as covariates. RESULTS: In the case-control study, 48% of long-term survivors were heterozygous for CCR5 delta 32 compared with 9% of progressors (odds ratio, 6.9 [95% CI, 1.9 to 24.8]). In the total study sample, CCR5 delta 32 heterozygotes had significantly delayed disease progression (P < 0.001; relative hazard, 0.4 [CI, 0.3 to 0.6]), a 1.5-fold slower decrease in CD4+ T-lymphocyte count (P = 0.01), and a 2.6-fold lower viral RNA load (P = 0.01) at approximately 2.3 years after seroconversion compared with CCR5 wild-type homozygotes. At the end of the study, both groups showed the same prevalence of syncytium-inducing HIV-1, but CCR5 delta 32 heterozygotes had a delayed conversion rate. The protective effect of CCR5 delta 32 heterozygosity was stronger in the presence of only non-syncytium-inducing HIV-1. The CCR5 genotype predicted disease progression independent of viral RNA load, CD4+ T-lymphocyte counts, T-lymphocyte function, and HIV-1 biological phenotype. CONCLUSIONS: The addition of CCR5 genotype to currently available laboratory markers may allow better estimation of the clinical course of HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

Characterization of RNA-mediated resistance to tomato spotted wilt virus in transgenic tobacco plants expressing NS(M) gene sequences.

Transgenic Nicotiana tabacum plants expressing RNA sequences of the tomato spotted wilt virus NS(M) gene, which encodes the putative viral movement protein, were found to be highly resistant to infection with the virus. Expression of untranslatable as well as anti-sense RNA of the NS(M) gene resulted in resistance levels as high as those in plants expressing translatable RNA sequences. For all three types of transgenic plants resistance levels of up to 100% were reached in the S2 progeny. These results indicate that the resistance mediated by the NS(M) gene is accomplished by expression of transcripts rather than protein in transgenic plants, similar to previously observed N gene-mediated resistance. Protoplast inoculations revealed that resistant plants expressing NS(M) are, in contrast to N transgenic resistant plants, not resistant at the cellular level. This suggests the RNA-mediated resistance mechanism against TSWV targets viral mRNAs rather than the viral genome.

Genes, Plant↗

Comparison of progression and non-progression in injecting drug users and homosexual men with documented dates of HIV-1 seroconversion. European Seroconverter Study and the Tricontinental Seroconverter Study.

OBJECTIVE: To compare the progression and non-progression of HIV infection among 418 injecting drug users (IDU) and 422 homosexual men with documented dates of HIV seroconversion from 12 cohorts. METHODS: Seroconversion dates were calculated for each subject using a cohort-specific estimate of the cumulative HIV seroincidence over calendar time. In survival analysis, we studied the progression from seroconversion to AIDS and death by risk group. We compared non-progression between both risk groups by evaluating annual CD4 decline over the 7 years following seroconversion among AIDS-free subjects. RESULTS: The relative hazard (RH) of AIDS for homosexual men compared with IDU was 1.54 before, and 1.21 after, adjusting for age at seroconversion and year of seroconversion. The risk of death from any cause for homosexual men compared with IDU increased over time since seroconversion. Fifty IDU died prior to AIDS, compared with seven homosexual men (unadjusted RH for homosexual men 0.10). Ignoring this pre-AIDS mortality, the crude RH of death for homosexual men compared with IDU was 2.05. Alter adjusting for age at seroconversion and year of seroconversion in multivariate analysis, the RH became 1.42. No differences in progression between subgroups aged 24 years or older could be demonstrated, but subjects < 24 years were found to be at a decreased risk. Proportions of non-progressors based on CD4 slope > or = 0 at 7 years following seroconversion were higher for IDU than for homosexual men. No differences were found in the proportion (approximately 5%) classified as non-progressors by criteria of both slope > or = 0 and absolute CD4 counts > 500 cells x 10(6)/l, even if pre-AIDS deaths and losses to follow-up were included. CONCLUSIONS: We found little evidence for an effect of risk group on progression and non-progression. Pre-AIDS mortality was much higher among IDU than homosexual men. Pre-AIDS mortality and a nonlinear age effect should be considered in planning interventions as well as studies comparing risk groups and modelling the epidemic.

Acquired Immunodeficiency Syndrome↗

Early and late HIV-1 RNA level and its association with other markers and disease progression in long-term AIDS-free homosexual men.

OBJECTIVE: To study the association between virological markers and clinical progression in individuals with long-term AIDS-free HIV infection. DESIGN: Seventy-seven HIV-infected participants in the Amsterdam cohort study who remained AIDS-free for at least 8 years were prospectively followed during that time and during a subsequent period in which 15 developed AIDS. METHODS: Serum HIV-1 RNA levels were evaluated at 1 and 8 years after study entry. Progression to AIDS following the 8 AIDS-free years was studied using Kaplan-Meier estimates and Cox proportional hazard analysis. RESULTS: HIV-1 RNA increased over time in a large proportion of these long-term AIDS-free men. Most subjects showed progressive immune system damage and/or clinical manifestations of HIV disease at year 8. High RNA levels at year 8 were significantly associated with symptomatic HIV Infection, low CD4+ T-cell count, p24 antigenaemia, low T-cell reactivity at year 8 as well as rapid annual CD4+ T-cell decline. High RNA level at year 1 was associated with high RNA levels at year 8 and low CD4+ T-cell count at year 1. In univariate analysis, RNA was associated with progression to AIDS after 8 years. In multivariate analysis, only the CD4+ T-cell count at year 8 remained significantly associated with progression to AIDS. CONCLUSIONS: In later stages of HIV infection, measures of immune deficiency may be more powerful prognostic markers than serum HIV-1 RNA level, indicating that optimal staging of the HIV-infected patient requires the combined use of RNA levels, CD4+ T-cell counts, and T-cell reactivity instead of RNA levels alone.

Acquired Immunodeficiency Syndrome↗

Has the rate of progression to AIDS changed in recent years?

OBJECTIVES: To investigate whether the rate of progression to AIDS has changed over time by testing an effect of the year of seroconversion on AIDS onset (Centers for Disease Control and Prevention 1987 revised classification), next to an effect of the calendar period of follow-up. DESIGN: French multicentre prospective study of 385 homosexual and heterosexual subjects and 231 subjects from a multicentre study of European injecting drug users (IDU), all with a documented date of HIV-1 seroconversion. METHOD: The effect of the year of seroconversion was compared by the log-rank test. Crude and adjusted relative hazard (ARH) were quantified using the Cox model. Calendar period of follow-up was studied separately for sexual exposure group and IDU and treated as a time-dependent variable in a Cox model. RESULTS: In the 616 study subjects the year of seroconversion was not significantly related to AIDS occurrence (n = 108); the ARH was 0.88 [95% confidence interval (CI), 0.56-1.38] for those who seroconverted in 1988-1989, and 1.17 (95% CI, 0.61-2.25) for those who seroconverted after 1989, compared with those who seroconverted before 1988. In the sexual exposure group, a clear trend towards less rapid progression to AIDS was observed in subjects followed in 1991-1992 (ARH, 0.49; 95% CI, 0.24-0.99) and after 1992 (ARH, 0.54; 95% CI; 0.24-1.21), compared with those followed before 1991. This favorable trend was not observed in IDU despite a significant decrease over time of Pneumocystis carinii pneumonia as AIDS-defining illness. Conversely to sexual exposure groups, the frequency of antiretroviral treatment (mainly zidovudine) prescription was still low during the most recent calendar periods in IDU when the CD4 count threshold of 200 x 10(6)/l was reached. CONCLUSIONS: No evidence was found of a change in the rate of progression to AIDS in subjects who seroconverted in recent years. Furthermore, conversely to sexual exposure groups, the lack of favorable trends in IDU users followed in recent years suggest that health-care systems are not always adapted to their lifestyles.

Acquired Immunodeficiency Syndrome↗

Completion of the impatiens necrotic spot virus genome sequence and genetic comparison of the L proteins within the family Bunyaviridae.

The nucleotide sequence of the large (L) genome segment of impatiens necrotic spot virus (INSV) has been determined, and herewith the complete nucleotide sequence of the whole, tripartite genome of this important tospovirus has been elucidated. The L RNA is 8776 nucleotides long and of negative polarity, containing one large ORF on the viral complementary strand. Comparison of the deduced amino acid sequence of the INSV L RNA primary translation product (330.3 kDa) with those of the L RNAs of other members of the family Bunyaviridae reveals that this protein represents the putative viral RNA-dependent RNA polymerase. A cluster dendrogram of the (putative) RNA polymerases indicates that the genera Tospovirus and Tenuivirus, though both encompassing ambisense plant-infecting viruses, have different affinities to the animal-infecting Bunyaviridae, tospoviruses being most closely related to the genus Bunyavirus, and tenuiviruses to the genus Phlebovirus.

Amino Acid Sequence↗

[Parasitic pruritus: bird mite zoonosis].

In three women with persistent pruritus, aged 49, 28 and 4 years, infestation with the bird or chicken mite (Dermanyssus gallinae) was demonstrated. These mites live in narrow openings and cracks close to the bird housing during the daytime. At night they attack the birds on whose blood they live. When their host disappears, they may attack men, notably when their breeding places are in or near houses. Mite bites result in urticarial and itchy papulovesicular skin eruptions. Treatment of bird mite infestation consists of removing the old nests. Treatment of the patients is symptomatic. Epizoonosis belongs in the differential diagnosis of pruritus; infestation with bird or chicken mites is one of the possibilities.

Adult↗

RNA-mediated virus resistance in transgenic plants.

In recent years the concept of pathogen-derived resistance (PDR) has been successfully exploited for conferring resistance against viruses in many crop plants. Starting with coat protein-mediated resistance, the range has been broadened to the use of other viral genes as a source of PDR. However, in the course of the efforts, often no clear correlation could be made between expression levels of the transgenes and observed virus resistance levels. Several reports mentioned high resistance levels using genes incapable of producing protein, but in these cases, even plants accumulating high amounts of transgene RNA were not most resistant. To accommodate these unexplained observations, a resistance mechanism involving specific breakdown of viral RNAs has been proposed. Recent progress towards understanding the RNA-mediated resistance mechanism and similarities with the co-suppression phenomenon will be discussed.

Gene Expression↗

Progressive biparietal atrophy: an atypical presentation of Alzheimer's disease.

OBJECTIVES: To define the clinical, neuropsychological, and radiological features of bilateral parietal lobe atrophy. METHODS: Four patients underwent a comprehensive longitudinal neuropsychological assessment, as well as MRI and HMPAO-SPECT. RESULTS: The consistent findings in the patients were early visuospatial problems, agraphia of a predominantly peripheral (or apraxic) type, and difficulty with bimanual tasks, all of which outweighted deficits in memory and language until later in the course of the illness. As the disease progressed, impairments in the phonological aspects of language and in auditory-verbal short term memory were often striking, perhaps reflecting spread from the parietal lobe to perisylvian language areas. Three patients went on to develop a global dementia and fulfilled the criteria for a clinical diagnosis of probable Alzheimer's disease; the fourth patient has only recently been identified. Neuroimaging disclosed bilateral parietal lobe atrophy (MRI) and hypoperfusion (SPECT), which was out of proportion to that seen elsewhere in the brain. One patient has died and had pathologically confirmed Alzheimer's disease with particular concentration in both superior parietal lobes. CONCLUSIONS: Bilateral biparietal atrophy is a recognisable clinical syndrome which can be the presenting feature of Alzheimer's disease. Although the label "posterior cortical atrophy" has been applied to such cases, review of the medical literature suggests that this broad rubric actually consists of two main clinical syndromes with features reflecting involvement of the occipitotemporal (ventral) and biparietal (dorsal) cortical areas respectively.

Aged↗

Alterations in plasma lipoproteins and apolipoproteins before the age of 40 in heterozygotes for lipoprotein lipase deficiency.

We have assessed the expression of heterozygosity for lipoprotein lipase (LPL) deficiency by studying a single large French Canadian family comprising 92 persons including 21 carriers of the catalytically defective P207L mutation. Phenotypic changes distinguishing heterozygotes from controls were seen early, before the age of 40 and often before 20 years of age. In the total cohort these changes included an elevation in the mean very low density (VLDL) and intermediate density lipoprotein (IDL) triglyceride (+69%; P = 0.01 and +40%; P = 0.001) and cholesterol (+51%; P = 0.03 and +67%; P = 0.007) and apoB levels but decreased HDL2 and HDL3 cholesterol, (-32%; P = 0.01 and -15%; P = 0.002 respectively). While the lipid compositions of VLDL and IDL were similar between heterozygotes and controls, the low density (LDL) and high density lipoproteins (HDL) of carriers were triglyceride enriched. Heterozygotes also had a markedly lower apoC-III ratio (apoC-III in supernatant/apoC-III in heparin precipitate) (1.46 vs. 3.86 P = 1 x 10(-4)) indicating a substantial enrichment of VLDL and IDL with apoC-III and depletion of HDL apoC-III supporting this ratio as an effective index for efficiency of lipolysis. LpA-I was markedly reduced (0.34 vs. 0.43 P = 1 x 10(-5)) showing that levels of this particle are partly dependent on LPL catalytic activity. Heterozygotes manifest from an early age with a markedly reduced HDL, LpA-I, apoC-III ratio and an increased TC/HDLc ratio which would predict a relatively increased risk of premature coronary artery disease, compared to their normal siblings.

Adult↗

Leucocytoclastic vasculitis induced by prolonged exercise.

Many people develop skin symptoms after long-distance walks, but little is known about the aetiology of these. In this study we took 11 biopsies from 10 long-distance walkers who walked 80 km. All biopsies originated from purpuric lesions on the lower legs, which had appeared during walking. In all 11 specimens, signs of a leucocytoclastic vasculitis were present with leucocytoclasis, exocytosis of erythrocytes and a granulocyte/mononuclear perivascular infiltrate. Immunofluorescence investigations showed deposition of C3c in many specimens and immunoglobulin M in some. The occurrence of a leucocytoclastic vasculitis after prolonged exercise may be explained by the existence of an exercise altered cutaneous microcirculation, complement activation and an altered immune function.

Complement C3c↗

Innervation of the lacrimal gland in the cynomolgous monkey: a retrograde tracing study.

Retrograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was used to study the localisation of neurons that innervate the lacrimal gland of the cynomolgous monkey. WGA-HRP-labelled neurons were localised in the ipsilateral trigeminal, superior cervical and ciliary ganglia and in the ipsilateral and contralateral pterygopalatine ganglia. In the trigeminal ganglion WGA-HRP-labelled somata were found in the ophthalmic part (18%) and the maxillary part (5%). Identification of labelled neurons in the ciliary and pterygopalatine ganglia indicates a dual parasympathetic innvervation of the lacrimal gland. There is no known pathway to account for the contralateral location or pterygopalatine neurons. These novel findings are incorporated in a concept of a neural control mechanism for the lacrimal gland.

Animals↗

Innervation of the palpebral conjunctiva and the superior tarsal muscle in the cynomolgous monkey: a retrograde fluorescent tracing study.

Retrograde fluorescent transport of Fast Blue (FB) and Diamidino Yellow (DY) was used to study the localisation of neurons that innervate the palpebral conjunctiva and the superior tarsal muscle in the cynomolgous monkey. Labelled cell bodies of sensory neurons including a few double labelled cell bodies were found in the ophthalmic part of the ipsilateral trigeminal ganglion. Labelled cell bodies of the sympathetic neurons including a few double labelled cell bodies were located in the middle and cranial part of the ipsilateral superior cervical ganglion, with a few in the contralateral ganglion. Labelled cell bodies of the parasympathetic neurons were all found in the ipsilateral pterygopalatine ganglion and randomly distributed. Neurons were disposed in the opthalmic part of the trigeminal and superior cervical ganglia, whereas parasympathetic neurons were distributed randomly. Cells of the nodose, ciliary, geniculate, otic and first 3 spinal ganglia were unlabelled. Tracing FB and DY from the palpebral conjunctiva and superior tarsal muscle respectively, revealed double labelled neurons in the trigeminal and superior cervical ganglia, probably indicating the presence of collaterals of axons serving both the palpebral conjunctiva and the superior tarsal muscle.

Animals↗